RESUMO
To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.
Assuntos
Aminoácidos , Corantes Fluorescentes , Nanopartículas , Placa Aterosclerótica , Espécies Reativas de Oxigênio , Placa Aterosclerótica/diagnóstico por imagem , Animais , Espécies Reativas de Oxigênio/metabolismo , Corantes Fluorescentes/química , Nanopartículas/química , Camundongos , Aminoácidos/química , Humanos , Medição de Risco , Imagem Óptica , Raios Infravermelhos , Células RAW 264.7RESUMO
The antioxidant defense mechanisms play a critical role in mitigating the deleterious effects of reactive oxygen species (ROS). Catalase stands out as a paramount enzymatic antioxidant. It efficiently catalyzes the decomposition of hydrogen peroxide (H2O2) into water and oxygen, a potentially harmful byproduct of cellular metabolism. This reaction detoxifies H2O2 and prevents oxidative damage. Catalase has been extensively studied as a therapeutic antioxidant. Its applications range from direct supplementation in conditions characterized by oxidative stress to gene therapy approaches to enhance endogenous catalase activity. The enzyme's stability, bioavailability, and the specificity of its delivery to target tissues are significant hurdles. Furthermore, studies employing conventional catalase formulations often face issues related to enzyme purity, activity, and longevity in the biological milieu. Addressing these challenges necessitates rigorous scientific inquiry and well-designed clinical trials. Such trials must be underpinned by sound experimental designs, incorporating advanced catalase formulations or novel delivery systems that can overcome existing limitations. Enhancing catalase's stability, specificity, and longevity in vivo could unlock its full therapeutic potential. It is necessary to understand the role of catalase in disease-specific contexts, paving the way for precision antioxidant therapy that could significantly impact the treatment of diseases associated with oxidative stress.
Assuntos
Antioxidantes , Catalase , Estresse Oxidativo , Catalase/metabolismo , Catalase/química , Humanos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Terapia Genética/métodosRESUMO
Soil salinization is a major abiotic stress factor that negatively impacts plant growth, development, and crop yield, severely limiting agricultural production and economic development. Cotton, a key cash crop, is commonly cultivated as a pioneer crop in regions with saline-alkali soil due to its relatively strong tolerance to salt. This characteristic renders it a valuable subject for investigating the molecular mechanisms underlying plant salt tolerance and for identifying genes that confer salt tolerance. In this study, focus was placed on examining a salt-tolerant variety, E991, and a salt-sensitive variety, ZM24. A combined analysis of transcriptomic data from these cotton varieties led to the identification of potential salt stress-responsive genes within the glutathione S-transferase (GST) family. These versatile enzyme proteins, prevalent in animals, plants, and microorganisms, were demonstrated to be involved in various abiotic stress responses. Our findings indicate that suppressing GhGSTF9 in cotton led to a notably salt-sensitive phenotype, whereas heterologous overexpression in Arabidopsis plants decreases the accumulation of reactive oxygen species under salt stress, thereby enhancing salt stress tolerance. This suggests that GhGSTF9 serves as a positive regulator in cotton's response to salt stress. These results offer new target genes for developing salt-tolerant cotton varieties.
Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Gossypium , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Arabidopsis/genética , Gossypium/genética , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Espécies Reativas de Oxigênio/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Estresse Fisiológico/genética , Plantas Tolerantes a Sal/genéticaRESUMO
Aerosol pollutants significantly cause health concerns. Herein, we established an original real-time aerosol exposure system that used a self-designed bionic-lung microfluidic chip. The chip features a 4 × 4 intersecting array within gas and liquid layers, creating 16 distinct microenvironments. A membrane situated between the layers offers attachment for cells and establishes a gas-liquid interface. This design provides a reliable screening capacity for investigating the biological effects of aerosol exposure in vitro by manipulating the gas and/or liquid conditions. Using this system, we validated that cigarette smoke (CS) aerosol triggered a concentration- and time-dependent reduction in cell viability and intracellular glutathione levels, accompanied by an increase in intracellular reactive oxygen species and Fe2+. Furthermore, CS aerosol significantly downregulated the expression of GPX4, SLC7A11, and FTL mRNA while inducing a notable increase in that of ACSL4 mRNA. Additionally, CS aerosol markedly stimulated the release of proinflammatory cytokines. Crucially, the ferroptosis inhibitor deferoxamine mesylate reversed these biological indicators. These results demonstrate that our novel bionic-lung chip presents a suitably achievable approach to investigate the biological effects induced by aerosol exposure.
Assuntos
Aerossóis , Ferroptose , Dispositivos Lab-On-A-Chip , Ferroptose/efeitos dos fármacos , Humanos , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Nicotiana/química , Fumaça , Glutationa/metabolismo , Gases/química , Células A549RESUMO
The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.
Assuntos
Hipertensão Intracraniana , Estresse Oxidativo , Animais , Ratos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/tratamento farmacológico , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Microcirculação , Circulação Cerebrovascular , Ratos Sprague-Dawley , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Infliximab/farmacologia , Infliximab/uso terapêutico , Modelos Animais de Doenças , Barreira Hematoencefálica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Microglia/metabolismoRESUMO
Reactive oxygen species (ROS) participate in almost all disorders, including cancer. Many factors, including aging, a high-fat diet, a stressful lifestyle, smoking, infection, genetic mutations, etc., lead to elevated levels of ROS. Prostate cancer, the most prevalent type of cancer in senior American men and the second leading cause of cancer mortality in American men, results from chronic oxidative stress. The doubled incident rate as well as the doubled mortality numbers of prostate cancer have persisted in African Americans in comparison with Caucasian Americans and other racial groups, indicating a prostate cancer disparity in African American men. In this review, we mainly focus on the latest findings on ROS in prostate cancer development and progression within the last five years to update our understanding in this area, as several comprehensive literature reviews addressing oxidative stress and/or inflammation in prostate cancer before 2020 are available. In addition to other known factors such as socioeconomic disadvantage, cultural mistrust of the health care system, etc. that are long-existing in the African American group, we also summarize the latest evidence that demonstrated high systemic oxidative stress and inflammation in African Americans for their potential contribution to the racial prostate cancer disparity in this population.
Assuntos
Negro ou Afro-Americano , Estresse Oxidativo , Neoplasias da Próstata , Espécies Reativas de Oxigênio , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/epidemiologia , Espécies Reativas de Oxigênio/metabolismo , Negro ou Afro-Americano/genética , População Negra/genética , Disparidades nos Níveis de Saúde , Inflamação/metabolismoRESUMO
Clinical therapies, including dermatology and oncology, require safe application. In vitro experiments allow only limited conclusions about in vivo effects, while animal studies in, e.g., rodents have ethical constraints at a large scale. Chicken embryos lack pain reception until day 15 postfertilization, making the in ovo model a suitable alternative to in vivo safety assessment. In addition, the hen's egg test on chorioallantoic membrane assay allows irritation potential analysis for topical treatments, but standardized analysis has been limited so far. Medical gas plasma is a topical, routine, approved dermatology treatment. Recent work suggests the potential of this technology in oncology. Its main mode of action is the release of various reactive species simultaneously. Intriguingly, varying plasma feed gas compositions generates customized reactive species profiles previously shown to be optimized for specific applications, such as skin cancer treatment. To support clinical implications, we developed a novel chicken embryo CAM scoring and study scheme and employed the model to analyze 16 different plasma feed gas settings generated by the atmospheric pressure plasmajet kINPen, along with common anticancer drugs (e.g., cisplatin) and physiological mediators (e.g., VEGF). Extensive gas- and liquid-phase plasma reactive species profiling was done and was found to have a surprisingly low correlation with irritation potential parameters. Despite markedly different reactive species patterns, feed gas-modulated kINPen plasma was equally tolerated compared to standard argon plasma. CAM irritation with gas plasmas but not anticancer agents was reversed 48 h after treatment, underlining the only temporary tissue effects of medical gas plasma. Our results indicate a safe therapeutic application of reactive species.
Assuntos
Antineoplásicos , Membrana Corioalantoide , Gases em Plasma , Animais , Gases em Plasma/química , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Humanos , Medição de Risco , Espécies Reativas de Oxigênio/metabolismo , GalinhasRESUMO
Airborne pathogens severely threaten public health worldwide. Air disinfection is essential to ensure public health. However, excessive use of disinfectants may endanger environmental and ecological security due to the residual disinfectants and their by-products. This study systematically evaluated disinfection efficiency, induction of multidrug resistance, and the underlying mechanisms of disinfectants (NaClO and H2O2) on airborne bacteria. The results showed that airborne bacteria were effectively inactivated by atomized NaClO (>160 µg/L) and H2O2 (>320 µg/L) after 15 min. However, some bacteria still survived after disinfection by atomized NaClO (0-80 µg/L) and H2O2 (0-160 µg/L), and they exhibited significant increases in antibiotic resistance. The whole-genome sequencing of the resistant bacteria revealed distinct mutations that were responsible for both antibiotic resistance and virulence. This study also provided evidences and insights into possible mechanisms underlying the induction of antibiotic resistance by air disinfection, which involved intracellular reactive oxygen species formation, oxidative stress responses, alterations in bacterial membranes, activation of efflux pumps, and the thickening of biofilms. The present results also shed light on the role of air disinfection in inducing antibiotic resistance, which could be a crucial factor contributing to the global spread of antibiotic resistance through the air.
Assuntos
Bactérias , Desinfetantes , Desinfecção , Peróxido de Hidrogênio , Peróxido de Hidrogênio/farmacologia , Desinfetantes/farmacologia , Desinfecção/métodos , Bactérias/efeitos dos fármacos , Bactérias/genética , Microbiologia do Ar , Biofilmes/efeitos dos fármacos , Hipoclorito de Sódio/farmacologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Antibacterianos/farmacologia , Cloro/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Biochar is currently garnering interest as an alternative to commercial fertilizer and as a tool to counteract global warming. However, its use is increasingly drawing attention, particularly concerning the fine dust that can be developed during its manufacture, transport, and use. This work aimed to assess the toxicity of fine particulate Biochar (Assuntos
Carvão Vegetal
, Poeira
, Animais
, Poeira/análise
, Masculino
, Humanos
, Ratos Wistar
, Espécies Reativas de Oxigênio/metabolismo
, Poluentes Atmosféricos/toxicidade
, Ratos
, Proliferação de Células/efeitos dos fármacos
, Trifosfato de Adenosina/metabolismo
, Estresse Oxidativo/efeitos dos fármacos
, Interleucina-8/metabolismo
, Material Particulado/toxicidade
RESUMO
Although di(2-ethylhexyl) terephthalate (DOTP) is being widely adopted as a non-phthalate plasticizer, existing research primarily focuses on human and rat toxicity. This leaves a significant gap in our understanding of their impact on microbial communities. This study assessed the biodegradation and toxicity of DOTP on microbes, focusing on its impact on biofilms and microbial metabolism using Rhodococcus ruber as a representative bacterial strain. DOTP is commonly found in mass fractions between 0.6 and 20% v/v in various soft plastic products. This study used polyvinyl chloride films (PVC) with varying DOTP concentrations (range 1-10% v/v) as a surface for analysis of biofilm growth. Cell viability and bacterial stress responses were tested using LIVE/DEAD™ BacLight™ Bacterial Viability Kit and by the detection of reactive oxygen species using CellROX™ Green Reagent, respectively. An increase in the volume of dead cells (in the plastisphere biofilm) was observed with increasing DOTP concentrations in experiments using PVC films, indicating the potential negative impact of DOTP on microbial communities. Even at a relatively low concentration of DOTP (1%), signs of stress in the microbes were noticed, while concentrations above 5% compromised their ability to survive. This research provides a new understanding of the environmental impacts of alternative plasticizers, prompting the need for additional research into their wider effects on both the environment and human health.
Assuntos
Biodegradação Ambiental , Biofilmes , Ácidos Ftálicos , Plastificantes , Espécies Reativas de Oxigênio , Plastificantes/toxicidade , Biofilmes/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Rhodococcus/metabolismo , Rhodococcus/efeitos dos fármacos , Cloreto de Polivinila/toxicidade , Dietilexilftalato/toxicidadeRESUMO
During plastic waste degradation into micro/nanoplastics (MNPLs) their physicochemical characteristics including surface properties (charge, functionalization, biocorona, etc.) can change, potentially affecting their biological effects. This paper focuses on the surface functionalization of MNPLs to determine if it has a direct impact on the toxicokinetic and toxicodynamic interactions in human umbilical vein endothelial cells (HUVECs), at different exposure times. Pristine polystyrene nanoplastics (PS-NPLs), as well as their carboxylated (PS-C-NPLs) and aminated (PS-A-NPLs) forms, all around 50 nm, were used in a wide battery of toxicological assays. These assays encompassed evaluations on cell viability, cell internalization, induction of intracellular reactive oxygen species (iROS), and genotoxicity. The experiments were conducted at a concentration of 100 µg/mL, chosen to ensure a high internalization rate across all treatments while maintaining a sub-toxic concentration. Our results show that all PS-NPLs are internalized by HUVECs, but the internalization dynamic depends on the particle's functionalization. PS-NPLs and PS-C-NPLs internalization modify the morphology of the cell increasing its inner complexity/granularity. Regarding cell toxicity, only PS-A-NPLs reduced cell viability. Intracellular ROS was induced by the three different PS-NPLs but at different time points. Genotoxic damage was induced by the three PS-NPLs at short exposures (2 h), but not for PS-C-NPLs at 24 h. Overall, this study suggests that the toxicological effects of PSNPLs on HUVEC cells are surface-dependent, highlighting the relevance of using human-derived primary cells as a target.
Assuntos
Sobrevivência Celular , Células Endoteliais da Veia Umbilical Humana , Microplásticos , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Microplásticos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Nanopartículas/toxicidade , Propriedades de Superfície , Poliestirenos/toxicidade , Células Endoteliais/efeitos dos fármacosRESUMO
We investigated the health conditions of the Mediterranean mussel Mytilus galloprovincialis recruited in the CO2 vents system of Castello Aragonese at Ischia Island (Mediterranean Sea). Individuals of M. galloprovincialis were sampled in three sites along the pH gradient (8.10, 7.7 and up to <7.4). Untargeted metabolomics and biochemical endpoints related to energetic metabolism, oxidative stress/damage, neurotoxicity and immune defense were analyzed. Corrosion of the valves occurred at low pH. A separation of the metabolome was observed along the pH gradient. Metabolites belonging to amino acids, nucleosides, lipids and organic osmolytes were significantly reduced in the organisms from the most acidified sites. The content of reactive oxygen species and the activity of glutathione peroxidase were reduced in organisms from the acidified sites compared to ambient pH, and no oxidative damage was induced. Overall results suggested the presence of an energy cost underpinning long-term survival in acidified conditions for this species.
Assuntos
Metabolismo Energético , Mytilus , Estresse Oxidativo , Animais , Concentração de Íons de Hidrogênio , Água do Mar/química , Mar Mediterrâneo , Metaboloma , Espécies Reativas de Oxigênio/metabolismo , Acidificação dos OceanosRESUMO
The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.
Assuntos
Cóclea , Molécula 1 de Adesão Intercelular , Ruído , Estresse Oxidativo , Ficocianina , Sinapses , Animais , Estresse Oxidativo/efeitos dos fármacos , Cobaias , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Cóclea/metabolismo , Cóclea/efeitos dos fármacos , Cóclea/patologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Ruído/efeitos adversos , Molécula 1 de Adesão Intercelular/metabolismo , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/patologia , Espécies Reativas de Oxigênio/metabolismo , Masculino , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/metabolismo , Gânglio Espiral da Cóclea/patologia , Peróxido de Hidrogênio/metabolismo , Células Ciliadas Auditivas Internas/efeitos dos fármacos , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Internas/patologia , Antioxidantes/farmacologia , Linhagem Celular , Perda Auditiva OcultaRESUMO
BACKGROUND: Salt stress is a multicomponent phenomenon; it includes many processes that directly or indirectly affect the plant. Attempts have been made to comprehensively consider the processes of salt stress in plants Triticum aestivum (variety Orenburgskaya 22) and Triticum durum (variety Zolotaya). METHODS: The study used methods of light and fluorescence microscopy, methods of immunofluorodetection, expression of DNA methyltransferase genes, genes of the ion transporter and superoxide dismutase families, as well as biochemical determination of total antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) reagent. RESULTS: According to morphometric indicators, the Orenburgskaya 22 variety showed greater tolerance to the action of 150 mM NaCl than the Zolotaya variety. The level of expression of genes of the HKT ion transporter family in the Orenburgskaya 22 variety is higher than in the Zolotaya variety. It was found that the expression of the DNA methyltransferase gene DRM2.1, which post-translationally methylates cytosine residues, is 22.3 times higher in Zolotaya compared to Orenburg 22 when exposed to salt. The accumulation of toxic ions is accompanied by an increase in reactive oxygen species (ROS) and increased damage to root tissue, especially in the Zolotaya variety. Using fluorescence microscopy using the Carboxy-H2DFF marker in the Orenburgskaya 22 variety at high NaCl concentrations, the highest fluorescence intensity was determined in the cap zone; in the Zolotaya variety-in the zones of the cap and root meristem. Excess ROS is more successfully removed in the Orenburgskaya 22 variety, which has a higher level of antioxidant activity (AOA), as well as the level of expression of the Cu/ZnSOD and MnSOD superoxide dismutase genes. Using programmed cell death (PCD) markers based on the release of cytochrome c from mitochondria into the cytoplasm, DNA breakage and the release of phosphatidylserine from mitochondria, the degree of damage to root cells was assessed in both wheat varieties. It has been proven that wheat cell death occurs through the mitochondrial pathway. It was noted that the salt-sensitive variety Zolotaya had a significant number of necrotic cells. CONCLUSION: Based on the data obtained, it was concluded that the Orenburgskaya 22 variety exhibits greater resistance to salinity than the Zolotaya variety. These data may be of practical importance for enhancing protective mechanisms under abiotic stress.
Assuntos
Tolerância ao Sal , Triticum , Triticum/genética , Triticum/metabolismo , Triticum/fisiologia , Tolerância ao Sal/genética , Regulação da Expressão Gênica de Plantas , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Photodynamic therapy (PDT) utilizes the potential of photosensitizing substances to absorb light energy and produce reactive oxygen species. Tetra-cationic porphyrins, which have organic or coordination compounds attached to their periphery, are heterocyclic derivatives with well-described antimicrobial and antitumoral properties. This is due to their ability to produce reactive oxygen species and their photobiological properties in solution. Consequently, these molecules are promising candidates as new and more effective photosensitizers with biomedical, environmental, and other biomedical applications. Prior to human exposure, it is essential to establish the toxicological profile of these molecules using in vivo models. In this study, we used Caenorhabditis elegans, a small free-living nematode, as a model for assessing toxic effects and predicting toxicity in preclinical research. We evaluated the toxic effects of porphyrins (neutral and tetra-cationic) on nematodes under dark/light conditions. Our findings demonstrate that tetra-methylated porphyrins (3TMeP and 4TMeP) at a concentration of 3.3⯵g/mL (1.36 and 0.93⯵M) exhibit high toxicity (as evidenced by reduced survival, development, and locomotion) under dark conditions. Moreover, photoactivated tetra-methylated porphyrins induce higher ROS levels compared to neutral (3TPyP and 4TPyP), tetra-palladated (3PdTPyP and 4PdTPyP), and tetra-platinated (3PtTPyP and 4PtTPyP) porphyrins, which may be responsible for the observed toxic effects.
Assuntos
Caenorhabditis elegans , Luz , Fármacos Fotossensibilizantes , Porfirinas , Animais , Caenorhabditis elegans/efeitos dos fármacos , Porfirinas/toxicidade , Porfirinas/química , Fármacos Fotossensibilizantes/toxicidade , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Cátions/toxicidade , Relação Dose-Resposta a DrogaRESUMO
Peroxiredoxin-1 (Prdx1) is a thiol-specific antioxidant enzyme that detoxifies reactive oxygen species (ROS) and regulates the redox status of cells. In this study, the Prdx1 cDNA sequence was isolated from the pre-established Amphiprion clarkii (A. clarkii) (AcPrdx1) transcriptome database and characterized structurally and functionally. The AcPrdx1 coding sequence comprises 597 bp and encodes 198 amino acids with a molecular weight of 22.1 kDa and a predicted theoretical isoelectric point of 6.3. AcPrdx1 is localized and functionally available in the cytoplasm and nucleus of cells. The TXN domain of AcPrdx1 comprises two peroxiredoxin signature VCP motifs, which contain catalytic peroxidatic (Cp-C52) and resolving cysteine (CR-C173) residues. The constructed phylogenetic tree and sequence alignment revealed that AcPrdx1 is evolutionarily conserved, and its most closely related counterpart is Amphiprion ocellaris. Under normal physiological conditions, AcPrdx1 was ubiquitously detected in all tissues examined, with the most robust expression in the spleen. Furthermore, AcPrdx1 transcripts were significantly upregulated in the spleen, head kidney, and blood after immune stimulation by polyinosinic:polycytidylic acid (poly (I:C)), lipopolysaccharide (LPS), and Vibrio harveyi injection. Recombinant AcPrdx1 (rAcPrdx1) demonstrated antioxidant and DNA protective properties in a concentration-dependent manner, as evidenced by insulin disulfide reduction, peroxidase activity, and metal-catalyzed oxidation (MCO) assays, whereas cells transfected with pcDNA3.1(+)/AcPrdx1 showed significant cytoprotective function under oxidative and nitrosative stress. Overexpression of AcPrdx1 in fathead minnow (FHM) cells led to a lower viral copy number following viral hemorrhagic septicemia virus (VHSV) infection, along with upregulation of several antiviral genes. Collectively, this study provides insights into the function of AcPrdx1 in defense against oxidative stressors and its role in the immune response against pathogenic infections in A. clarkii.
Assuntos
Proteínas de Peixes , Peroxirredoxinas , Filogenia , Vibrioses , Animais , Peroxirredoxinas/metabolismo , Peroxirredoxinas/genética , Peroxirredoxinas/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Proteínas de Peixes/imunologia , Vibrioses/imunologia , Poli I-C/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata , Vibrio/imunologia , Vibrio/fisiologia , Clonagem Molecular , Sequência de Aminoácidos , Perciformes/imunologia , Lipopolissacarídeos/imunologia , Alinhamento de Sequência , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVES: Fasciolosis is of significant economic and public health importance worldwide. The lack of a successful vaccine and emerging resistance in flukes to the drug of choice, triclabendazole, has initiated the search for alternative approaches. In recent years, metallic nanoparticles have been extensively investigated for their anthelmintic effects. This study investigates the in vitro anthelmintic activity of copper oxide and zinc oxide nanoparticles against Fasciola hepatica. METHODS: The in vitro study was based on egg hatchability test (EHA), adult motility inhibition tests, DNA damage, ROS levels, as well as several biomarkers of oxidative stress, including glutathione peroxidase (GSH) and glutathione S-transferase (GST), superoxide dismutase (SOD) and malondialdehyde (MDA). For this purpose, different concentrations of copper oxide nanoparticles (CuO-NPs) and Zinc oxide nanoparticles (ZnO-NPs) (1, 4, 8, 12, and 16 ppm) were used to evaluate the anthelmintic effect on different life stages, including egg and adults of Fasciola hepatica, over 24 h. RESULTS: In vitro treatment of F. hepatica worms with both CuO-NPs and ZnO-NPs could significantly increase ROS production and oxidative stress induction (decreased SOD, GST and GSH and increased MDA) compared to control group. CONCLUSIONS: Based on the results, it seems that CuO-NPs and ZnO-NPs may be effective in the control and treatment of F. hepatica infection. Further research is needed to investigate their potential for in vivo use in the treatment of parasitic infections.
Assuntos
Anti-Helmínticos , Fasciola hepatica , Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Óxido de Zinco/farmacologia , Cobre/farmacologia , Espécies Reativas de Oxigênio , Estresse Oxidativo , Anti-Helmínticos/farmacologia , Dano ao DNA , Superóxido Dismutase/metabolismo , BiomarcadoresRESUMO
This paper presents a custom made small rover based surveying, mapping and building information modeling solution. Majority of the commercially available mobile surveying systems are larger in size which restricts their maneuverability in the targeted indoor vicinities. Furthermore their functional cost is unaffordable for low budget projects belonging to developing markets. Keeping in view these challenges, an economical indigenous rover based scanning and mapping system has developed using orthogonal integration of two low cost RPLidar A1 laser scanners. All the instrumentation of the rover has been interfaced with Robot Operating System (ROS) for online processing and recording of all sensorial data. The ROS based pose and map estimations of the rover have performed using Simultaneous Localization and Mapping (SLAM) technique. The perceived class 1 laser scans data belonging to distinct vicinities with variable reflective properties have been successfully tested and validated for required structural modeling. Systematically the recorded scans have been used in offline mode to generate the 3D point cloud map of the surveyed environment. Later the structural planes extraction from the point cloud data has been done using Random Sampling and Consensus (RANSAC) technique. Finally the 2D floor plan and 3D building model have been developed using point cloud processing in appropriate software. Multiple interiors of existing buildings and under construction indoor sites have been scanned, mapped and modelled as presented in this paper. In addition, the validation of the as-built models have been performed by comparing with the actual architecture design of the surveyed buildings. In comparison to available surveying solutions present in the local market, the developed system has been found faster, accurate and user friendly to produce more enhanced structural results with minute details.
Assuntos
Orçamentos , Computação em Nuvem , Espécies Reativas de Oxigênio , Consenso , LasersRESUMO
Resistance evolution during exposure to non-lethal levels of antibiotics is influenced by various stress responses of bacteria which are known to affect growth rate. Here, we aim to disentangle how the interplay between resistance development and associated fitness costs is affected by stress responses. We performed de novo resistance evolution of wild-type strains and single-gene knockout strains in stress response pathways using four different antibiotics. Throughout resistance development, the increase in minimum inhibitory concentration (MIC) is accompanied by a gradual decrease in growth rate, most pronounced in amoxicillin or kanamycin. By measuring biomass yield on glucose and whole-genome sequences at intermediate and final time points, we identified two patterns of how the stress responses affect the correlation between MIC and growth rate. First, single-gene knockout E. coli strains associated with reactive oxygen species (ROS) acquire resistance faster, and mutations related to antibiotic permeability and pumping out occur earlier. This increases the metabolic burden of resistant bacteria. Second, the ΔrelA knockout strain, which has reduced (p)ppGpp synthesis, is restricted in its stringent response, leading to diminished growth rates. The ROS-related mutagenesis and the stringent response increase metabolic burdens during resistance development, causing lower growth rates and higher fitness costs.
Assuntos
Antibacterianos , Escherichia coli , Escherichia coli/genética , Espécies Reativas de Oxigênio/metabolismo , Resistência Microbiana a Medicamentos , Antibacterianos/farmacologia , Estresse OxidativoRESUMO
Abstract: Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality. To elucidate the biological basis of such effects, we employed an acute in vitro exposure model in which the spermatozoa of adult male mice were exposed to a cocktail of PFAS chemicals at environmentally relevant concentrations. We hypothesized that direct PFAS treatment of spermatozoa would induce reactive oxygen species generation and compromise the functional profile and DNA integrity of exposed cells. Despite this, post-exposure functional testing revealed that short-term PFAS exposure (3 h) did not elicit a cytotoxic effect, nor did it overtly influence the functional profile, capacitation rate, or the in vitro fertilization ability of spermatozoa. PFAS treatment of spermatozoa did, however, result in a significant delay in the developmental progression of the day 4 pre-implantation embryos produced in vitro. This developmental delay could not be attributed to a loss of sperm DNA integrity, DNA damage, or elevated levels of intracellular reactive oxygen species. When considered together, the results presented here raise the intriguing prospect that spermatozoa exposed to a short-term PFAS exposure period potentially harbor an alternate stress signal that is delivered to the embryo upon fertilization. Lay summary: PFAS are synthetic chemicals widely used in non-stick cookware, food packaging, and firefighting foam. Such extensive use has led to concerning levels of environmental contamination and reports of associations with a spectrum of negative health outcomes, including testicular cancer and reduced semen quality. To investigate the effects of PFAS on male reproduction, we incubated mouse sperm in a cocktail of nine PFAS at environmentally relevant concentrations before checking for a range of functional outcomes. This treatment strategy was not toxic to the sperm; it did not kill them or reduce their motility, nor did it affect their fertilization capacity. However, we did observe developmental delays among pre-implantation embryos created using PFAS-treated sperm. Such findings raise the intriguing prospect that PFAS-exposed sperm harbor a form of stress signal that they deliver to the embryo upon fertilization.