RESUMO
Difenoconazole (DFZ) is a fungicidal pesticide extensively employed for the management of fungal diseases in fruits, vegetables, and cereal crops. However, its potential environmental impact cannot be ignored, as DFZ accumulation is able to lead to aquatic environment pollution and harm to non-target organisms. Quercetin (QUE), a flavonoid abundant in fruits and vegetables, possesses antioxidant and anti-inflammatory properties. In this article, carp were exposed to 400 mg/kg QUE and/or 0.3906 mg/L DFZ for 30 d to investigate the effect of QUE on DFZ-induced respiratory toxicity in carp. Research shows that DFZ exposure increases reactive oxygen species (ROS) production in the carp's respiratory system, leading to oxidative stress, inflammation, and damage to gill tissue and tight junction proteins. Further research demonstrates that DFZ induces mitochondrial dynamic imbalance and gill cell apoptosis. Notably, QUE treatment significantly reduces ROS levels, alleviates oxidative stress and inflammation, and mitigates mitochondrial dynamics imbalance and mitochondrial apoptosis. This study emphasizes the profound mechanism of DFZ toxicity to the respiratory system of common carp and the beneficial role of QUE in mitigating DFZ toxicity. These findings contribute to a better understanding of pesticide risk assessment in aquatic systems and provide new insights into strategies to reduce their toxicity.
Assuntos
Carpas , Dioxolanos , Praguicidas , Triazóis , Animais , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Dinâmica Mitocondrial , Carpas/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo , Inflamação , Sistema Respiratório , ApoptoseRESUMO
Synthetic antioxidants, including synthetic phenolic antioxidants (SPAs), amine antioxidants (AAs), and organophosphite antioxidants (OPAs), are essential additives for preventing oxidative aging in various industrial and consumer products. Increasing attention has been paid to the environmental contamination caused by these chemicals, but our understanding of synthetic antioxidants is generally limited compared to other emerging contaminants such as plasticizers and flame retardants. Many people spend a significant portion (normally greater than 80%) of their time indoors, meaning that they experience widespread and persistent exposure to indoor contaminants. Thus, this Perspective focuses on the problem of synthetic antioxidants as indoor environmental contaminants. The wide application of antioxidants in commercial products and their demonstrated toxicity make them an important family of indoor contaminants of emerging concern. However, significant knowledge gaps still need to be bridged: novel synthetic antioxidants and their related transformation products need to be identified in indoor environments, different dust sampling strategies should be employed to evaluate human exposure to these contaminants, geographic scope and sampling scope of research on indoor contamination should be broadened, and the partition coefficients of synthetic antioxidants among different media need to be investigated.
Assuntos
Poluição do Ar em Ambientes Fechados , Retardadores de Chama , Humanos , Antioxidantes , Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental , Fenóis , Monitoramento Ambiental , Poeira/análiseRESUMO
Photoinitiators (PIs) are a family of anthropogenic chemicals used in polymerization systems that generate active substances to initiate polymerization reactions under certain radiations. Although polymerization is considered a green method, its wide application in various commercial products, such as UV-curable inks, paints, and varnishes, has led to ubiquitous environmental issues caused by PIs. In this study, we present an overview of the current knowledge on the environmental occurrence, human exposure, and toxicity of PIs and provide suggestions for future research based on numerous available studies. The residual concentrations of PIs in commercial products, such as food packaging materials, are at microgram per gram levels. The migration of PIs from food packaging materials to foodstuffs has been confirmed by more than 100 reports of food contamination caused by PIs. Furthermore, more than 20 PIs have been detected in water, sediment, sewage sludge, and indoor dust collected from Asia, the United States, and Europe. Human internal exposure was also confirmed by the detection of PIs in serum. In addition, PIs were present in human breast milk, indicating that breastfeeding is an exposure pathway for infants. Among the most available studies, benzophenone is the dominant congener detected in the environment and humans. Toxicity studies of PIs reveal multiple toxic end points, such as carcinogenicity and endocrine-disrupting effects. Future investigations should focus on synergistic/antagonistic toxicity effects caused by PIs coexposure and metabolism/transformation pathways of newly identified PIs. Furthermore, future research should aim to develop "greener" PIs with high efficiency, low migration, and low toxicity.
Assuntos
Poeira , Embalagem de Alimentos , Feminino , Humanos , Ásia , Benzofenonas/química , ÁguaRESUMO
The increasing concern over environmental pollution caused by the pesticide avermectin used in aquaculture has attracted significant attention. The use of avermectin, a neurotoxic pesticide, in aquatic environments leads to toxic effects on non-target organisms, particularly causing harm to fish. The phenolic compound ferulic acid possesses excellent anti-inflammatory and antioxidant capabilities. This study was conducted by establishing a chronic exposure experiment to avermectin, proposes the use of ferulic acid as a dietary additive to protect the carp brain from damage caused by exposure to avermectin. Furthermore, it investigates the anti-inflammatory and antioxidant effects of ferulic acid in the carp brain under chronic exposure to avermectin. The experimental results demonstrate that ferulic acid can alleviate brain tissue inflammation and oxidative stress by modulating the Nrf2/Keap1 and NF-κB signaling pathways. It protects the carp brain from chronic avermectin-induced damage, preserves the integrity of the carp blood-brain barrier, enhances the levels of feeding factors, and thereby alleviates carp growth inhibition. These findings provide new therapeutic strategies and a theoretical foundation for the sustainable development of carp aquaculture.
Assuntos
Carpas , Praguicidas , Animais , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Imunidade Inata , Carpas/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Transdução de Sinais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Anti-Inflamatórios , Encéfalo/metabolismo , Proteínas de Peixes/metabolismoRESUMO
Avermectin is widely used as an important insecticide in agricultural production, but it also shows strong toxicity to non-target organisms. Quercetin is a natural flavonoid that is widely used due to its good anti-inflammatory and antioxidant effects. We believe that quercetin may have a potential therapeutic effect on avermectin poisoning. This experiment was proposed to observe the effect of quercetin on the toxic response to avermectin by observing the toxic response caused by avermectin in the brain of carp. In this project, 60 carp were studied as control group (Control), quercetin administration group (QUE), avermectin exposure group (AVM) and quercetin treatment avermectin exposure group (QUE + AVM) with different interventions to study the effect of quercetin on avermectin. The carp brain tissues were stained and simultaneously analyzed for blood-brain barrier (BBB), oxidative stress indicators, inflammatory factors, and apoptosis using qPCR technique. The results of the study indicate that avermectin exhibits a neurotoxic mechanism of action in fish by decreasing the transcript levels of tight junction protein-related genes, which in turn leads to the rupture of the BBB in the carp brain tissue. Avermectin induced apoptosis in carp brain tissue by increasing oxidative stress response and promoting inflammatory cell infiltration. Quercetin could reduce the accumulation of reactive oxygen species (ROS) in the brain tissue of carp caused by avermectin exposure toxicity, maintain redox homeostasis, reduce inflammatory response, and protect brain tissue cells from apoptosis. The present study confirmed the therapeutic and protective effects of quercetin on neurotoxicity in carp caused by avermectin exposure.
Assuntos
Carpas , Quercetina , Animais , Quercetina/farmacologia , Antioxidantes/farmacologia , Estresse Oxidativo , Encéfalo , ApoptoseRESUMO
As a kind of unicellular eukaryotic protozoa, Tetrahymena is located at the bottom of the aquatic food webs and plays an essential role in the bioaccumulation of mercury (Hg). To track Hg in individual Tetrahymena, a capillary single-cell inductively coupled plasma mass spectrometry (ICPMS) online system was developed. The experimental and instrumental conditions were optimized to ensure the signal detected was the Hg uptake in individual Tetrahymena. Moreover, a quantitative method was established and validated by detecting Hg2+ standard solutions. The limit of quantity was calculated to be approximately 3.8 × 10-15 g Hg/cell, and the detection limit for Hg2+ exposure of Tetrahymena was 0.05 µg/L. By using the proposed method, we found the peak became wider with increasing of exposure concentrations, indicating the accumulated Hg by different Tetrahymena varied greatly, and the difference was more significant at higher exposure concentration. This novel method has the advantages of high sensitivity and real-time detection in individual Tetrahymena, and it could be widely used for further tracking the accumulation of mercury and other metals at the single cell level.
Assuntos
Mercúrio/análise , Análise de Célula Única , Tetrahymena/química , Espectrometria de Massas/instrumentação , Análise de Célula Única/instrumentação , Tetrahymena/citologiaRESUMO
BACKGROUND: The present study aims to analyze the serum level of glucose 6-phosphate isomerase (GPI) in patients with knee osteoarthritis (KOA) and evaluate its value in the diagnosis of KOA. METHODS: One hundred patients with confirmed KOA were selected and 100 healthy people in the same period were selected as the control group. ELISA assay was performed to detect the serum GPI level of the subjects. The concentrations of GPI were also analyzed according the severity of KOA. Pearson's correlation was used to analyze the correlation between serum GPI and clinical index in diagnosing KOA. RESULTS: We showed novel data that the concentration of GPI in KOA patients was significantly enhanced compared to controls. Furthermore, the concentration of GPI was highest in the severe group, followed by that in moderate group and mild group. Pearson's correlation assay indicated a positive correlation between serum GPI and the severity of KOA. Meanwhile, a positive correlation was identified between serum GPI concentration and C-reactive protein (CRP) as well as erythrocyte sedimentation rate (ESR) in KOA patients. Receiver operating characteristic (ROC) analysis showed that serum GPI could screen KOA patients from controls. CONCLUSIONS: Collectively, elevated serum GPI concentration contributed to the progression of KOA, and targeting GPI may be useful for the therapy of KOA.
Assuntos
Glicemia , Osteoartrite do Joelho , Biomarcadores , Glucose-6-Fosfato Isomerase , Humanos , Osteoartrite do Joelho/diagnóstico , Curva ROCRESUMO
Amyloid beta 42 (Aß1-42)-induced oxidative stress causes the death of neuronal cells and is involved in the development of Alzheimer's disease. Oxymatrine (OMT) inhibits oxidative stress. In this study, we investigated the effect of OMT on Aß1-42-induced neurotoxicity in vivo and in vitro. In the Morris water maze test, OMT significantly decreased escape latency and increased the number of platform crossings. In vitro, OMT markedly increased cell viability and superoxide dismutase activity. Moreover, OMT decreased lactate dehydrogenase leakage, malondialdehyde content, and reactive oxygen species in a dose-dependent manner. OMT upregulated the ratio of Bcl-2/Bax and downregulated the level of caspase-3. Furthermore, OMT inhibited the activation of MAP kinase (ERK 1/2, JNK) and nuclear factor κB. In summary, OMT may potentially be used in the treatment of Alzheimer's disease.
Assuntos
Alcaloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Quinolizinas/farmacologia , Alcaloides/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Animais , Células Cultivadas , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Cultura Primária de Células , Quinolizinas/uso terapêutico , Ratos , Ratos Sprague-DawleyRESUMO
Avermectin, a widely used deworming drug, poses a significant threat to fisheries. Silybin is recognized for its antioxidant and anti-inflammatory properties. The kidney, being crucial for fish survival, plays a vital role in maintaining ion balance, nitrogen metabolism, and hormone regulation. While residual avermectin in water could pose a risk to carp (Cyprinus carpio), it remains unclear whether silybin can alleviate the renal tissue toxicity induced by avermectin in this species. In current study, we developed a model of long-term exposure of carp to avermectin to investigate the potential protective effect of silybin against avermectin-induced nephrotoxicity. The results indicated that avermectin induced renal inflammation, oxidative stress, ferroptosis, and autophagy in carp. Silybin suppressed the mRNA transcript levels of pro-inflammatory factors, increased catalase (CAT) activity, reduced glutathione (GSH) activity, diminished reactive oxygen species (ROS) accumulation in renal tissues, and promoted the activation of the Nrf2-Keap1 signaling pathway. Furthermore, the transcript levels of ferroptosis-associated proteins, including gpx4 and slc7a11, were significantly reduced, while those of cox2, ftl, and ncoa4 were elevated. The transcript levels of autophagy-related genes, including p62 and atg5, were also regulated. Network pharmacological analysis revealed that silybin inhibited ROS accumulation and mitigated avermectin-induced renal inflammation, oxidative stress, ferroptosis, and autophagy in carp through the involvement of PPAR-γ. Silybin exerted its anti-inflammatory effect through the NF-κB pathway and antioxidant effect through the Nrf2-Keap1 pathway, induced renal cell iron efflux through the SLC7A11/GSH/GPX4, and suppressed autophagy initiation via the PI3K/AKT pathway. This study provides evidence of the protective effect of silybin against avermectin-induced nephrotoxicity in carp, highlighting its potential as a therapeutic agent to alleviate the adverse effects of avermectin exposure in fish.
Assuntos
Autofagia , Carpas , Ferroptose , Ivermectina , Rim , Estresse Oxidativo , PPAR gama , Silibina , Animais , Autofagia/efeitos dos fármacos , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Silibina/farmacologia , PPAR gama/metabolismo , PPAR gama/genética , Rim/efeitos dos fármacos , Rim/patologia , Poluentes Químicos da Água/toxicidade , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Doenças dos Peixes/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismoRESUMO
Sepsis is a systemic inflammatory disease that is caused by a dysregulated host response to infection and is a life-threatening organ dysfunction that affects many organs, which includes the colon. Mounting evidence suggests that sepsis-induced colonic damage is a major contributor to organ failure and cellular dysfunction. Monotropein (MON) is the major natural compound in the iris glycoside that is extracted from Morendae officinalis radix, which possesses the potent pharmacological activities of anti-inflammatory and antioxidant properties. This research evaluated whether MON is able to alleviate septic colonic injury in mice by cecal ligation and puncture. Colonic tissues were analyzed using histopathology, immunofluorescence, quantitative real-time polymerase chain reaction, and Western blot methods. It was initially discovered that MON reduced colonic damage in infected mice, in addition to inflammation, apoptosis, and oxidative stress in colonic tissues, while it activated autophagy, with the NRF2/keap1 and PINK1/Parkin pathways also being activated. Through the stimulation of NCM460 cells with lipopolysaccharides, an in vitro model of sepsis was created as a means of further elucidating the potential mechanisms of MON. In the in vitro model, it was found that MON could still activate the NRF2/keap1, PINK1/Parkin, and autophagy pathways. However, when MON was paired with the NRF2 inhibitor ML385, it counteracted MON-induced activation of PINK1/Parkin and autophagy, while also promoting inflammatory response and apoptosis in NCM460 cells. Therefore, the data implies that MON could play a therapeutic role through the activation of the NFR2/PINK pathway as a means of inducing autophagy to alleviate the oxidative stress in colonic tissues that is induced by sepsis, which will improve inflammation and apoptosis in colonic tissues.
Assuntos
Iridoides , Fator 2 Relacionado a NF-E2 , Sepse , Camundongos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Inflamação/tratamento farmacológico , Autofagia , Sepse/complicações , Sepse/tratamento farmacológico , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismoRESUMO
BACKGROUND: To investigate the effect of Gypenoside XLIX (Gyp-XLIX) on acute splenic injury (ASI) induced by cecal ligation and puncture (CLP) in septic mice, a study was conducted. METHODS: Sixty healthy mice were randomly divided into six groups: the NC group, the Sham group, the Sham + Gyp-XLIX group, the CLP group, the CLP + Gyp-XLIX group, and the CLP + Dexamethasone (DEX) group. The NC group did not undergo any operation, while the rest of the groups underwent CLP to establish the sepsis model. The Sham group only underwent open-abdominal suture surgery without cecum puncture. After the operation, the groups were immediately administered the drug for a total of 5 days. Various methods such as hematoxylin and eosin (HE) staining, biochemical kits, qRT-PCR, and reactive oxygen species (ROS) were used for analysis. RESULTS: The results demonstrated that Gyp-XLIX effectively mitigated the splenic histopathological damage, while reducing the malondialdehyde (MDA) lipid peroxidation index and enhancing the antioxidant activities of catalase (CAT), glutathione (GSH) and total antioxidant capacity (T-AOC). The utilization of Dihydroethidium (DHE) fluorescent probe revealed that Gyp-XLIX inhibited the acute splenic accumulation of ROS induced by CLP in septic mice. Further investigations revealed that Gyp-XLIX exhibited a down-regulatory effect on the protein levels of inflammatory mediators iNOS and COX-2, consequently leading to the suppression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß. Additionally, it up-regulated the expression of anti-inflammatory factor IL-10. CONCLUSION: In conclusion, Gyp-XLIX was significantly effective in attenuating CLP-induced acute splenic inflammation and oxidative stress in septic mice.
Assuntos
Antioxidantes , Saponinas , Sepse , Camundongos , Animais , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Inflamação/tratamento farmacológico , Estresse Oxidativo , Fator de Necrose Tumoral alfa/farmacologia , Glutationa , Sepse/tratamento farmacológicoRESUMO
Synthetic antioxidants (AOs) are commonly used in everyday items and industrial products to inhibit oxidative deterioration. However, the presence of AOs in food packaging and packaged foods has not been thoroughly documented. Moreover, studies on human exposure to AOs through skin contact with packaging or ingesting packaged foods are limited. In this study, we analyzed twenty-three AOs-including synthetic phenolic antioxidants (SPAs) and organophosphite antioxidants (OPAs)-along with six transformation products in various food samples and their packaging materials. We found AOs in food products at concentrations ranging from 1.30 × 103 to 1.77 × 105 ng/g, which exceeded the levels in both outer packaging (6.05 × 102-3.07 × 104 ng/g) and inner packaging (2.27 × 102-1.09 × 105 ng/g). The most common AOs detected in foodstuffs were tris(2,4-di-tert-butylphenyl) phosphate (AO168O), butylated hydroxytoluene (BHT), and octadecyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (AO1076), together constituting 95.7 % of the total AOs found. Our preliminary exposure assessment revealed that dietary exposure-estimated at a median of 2.55 × 104 ng/kg body weight/day for children and 1.24 × 104 ng/kg body weight/day for adults-is a more significant exposure route than dermal contact with packaging. Notably, four AOs were identified in food for the first time, with BHT making up 76.8 % and 67.6 % of the total BHT intake for children and adults, respectively. These findings suggest that food consumption is a significant source of BHT exposure. The estimated daily intakes of AOs via consumption of foodstuffs were compared with the recommended acceptable daily intake to assess the risks. This systematic investigation into AOs contributes to understanding potential exposure and health risks associated with AOs in packaged foods. It emphasizes the need for further evaluation of human exposure to these substances.
Assuntos
Antioxidantes , Embalagem de Alimentos , Humanos , Antioxidantes/análise , Exposição Dietética/análise , Dieta , Exposição Ambiental/análise , Adulto , Contaminação de Alimentos/análiseRESUMO
The increasing use of phthalate acid esters (PAEs) in various applications has inevitably led to their widespread presence in the aquatic environment. This presents a considerable threat to plants. However, the interactions between PAEs and plants in the aquatic environment have not yet been comprehensively reviewed. In this review, the properties, occurrence, uptake, transformation, and toxic effects of PAEs on plants in the aquatic environment are summarized. PAEs have been prevalently detected in the aquatic environment, including surface water, groundwater, seawater, and sediment, with concentrations ranging from the ng/L or ng/kg to the mg/L or mg/kg range. PAEs in the aquatic environment can be uptake, translocated, and metabolized by plants. Exposure to PAEs induces multiple adverse effects in aquatic plants, including growth perturbation, structural damage, disruption of photosynthesis, oxidative damage, and potential genotoxicity. High-throughput omics techniques further reveal the underlying toxicity molecular mechanisms of how PAEs disrupt plants on the transcription, protein, and metabolism levels. Finally, this review proposes that future studies should evaluate the interactions between plants and PAEs with a focus on long-term exposure to environmental PAE concentrations, the effects of PAE alternatives, and human health risks via the intake of plant-based foods.
Assuntos
Ésteres , Ácidos Ftálicos , Plantas , Poluentes Químicos da Água , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Ésteres/toxicidade , Plantas/efeitos dos fármacos , Plantas/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Photoinitiators (PIs) are chemical additives that generate active substances, such as free radicals to initiate photopolymerization. Traditionally, polymerization has been considered a green technique that seldomly generates contaminants. However, many researches have confirmed toxicity effects of PIs, such as carcinogenicity, cytotoxicity, endocrine disrupting effects. Surprisingly, we found high levels of PIs in indoor dust. Our analysis revealed comparable levels of PIs in dust from printing shops (geometric mean, GM: 1.33 ×103 ng/g) and control environments (GM: 874 ng/g), underscoring the widespread presence of PIs across various settings. Alarmingly, in dust samples from nail salons, PIs were detected at total concentrations ranging from 610 to 1.04 × 107 ng/g (GM: 1.87 ×105 ng/g), significantly exceeding those in the control environments (GM: 1.43 ×103 ng/g). Nail salon workers' occupational exposure to PIs through dust ingestion was estimated at 4.86 ng/kg body weight/day. Additionally, an in vitro simulated digestion test suggested that between 10 % and 42 % of PIs present in ingested dust could become bioaccessible to humans. This is the first study to report on PIs in the specific environments of nail salons and printing shops. This study highlights the urgent need for public awareness regarding the potential health risks posed by PIs to occupational workers, marking an important step towards our understanding of environmental pollution caused by PIs.
Assuntos
Poeira , Exposição Ocupacional , Poeira/análise , Exposição Ocupacional/análise , Humanos , Medição de Risco , Poluição do Ar em Ambientes Fechados/análise , Indústria da Beleza , Poluentes Ocupacionais do Ar/análise , Poluentes Ocupacionais do Ar/toxicidadeRESUMO
To elucidate the potential risks of the toxic pollutant mercury (Hg) in polar waters, the study of accumulated Hg in fish is compelling for understanding the cycling and fate of Hg on a regional scale in Antarctica. Herein, the Hg isotopic compositions of Antarctic cod Notothenia coriiceps were assessed in skeletal muscle, liver, and heart tissues to distinguish the differences in Hg accumulation in isolated coastal environments of the eastern (Chinese Zhongshan Station, ZSS) and the antipode western Antarctica (Chinese Great Wall Station, GWS), which are separated by over 4000 km. Differences in odd mass-independent isotope fractionation (odd-MIF) and mass-dependent fractionation (MDF) across fish tissues were reflection of the specific accumulation of methylmercury (MeHg) and inorganic Hg (iHg) with different isotopic fingerprints. Internal metabolism including hepatic detoxification and processes related to heart may also contribute to MDF. Regional heterogeneity in iHg end-members further provided evidence that bioaccumulated Hg origins can be largely influenced by polar water circumstances and foraging behavior. Sea ice was hypothesized to play critical roles in both the release of Hg with negative odd-MIF derived from photoreduction of Hg2+ on its surface and the impediment of photochemical transformation of Hg in water layers. Overall, the multitissue isotopic compositions in local fish species and prime drivers of the heterogeneous Hg cycling and bioaccumulation patterns presented here enable a comprehensive understanding of Hg biogeochemical cycling in polar coastal waters.
Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Mercúrio/análise , Regiões Antárticas , Isótopos de Mercúrio/análise , Bioacumulação , Camada de Gelo , Monitoramento Ambiental , Compostos de Metilmercúrio/metabolismo , Peixes/metabolismo , Isótopos , Água/metabolismo , Poluentes Químicos da Água/análiseRESUMO
Background: Patients with initially unresectable colorectal cancer liver metastases (IU-CRLM) might benefit from using an effective systemic treatment followed by resection of liver metastases but the curative success rate is quite low. Indeed, nearly one-third of patients exhibit early recurrence within the first 6 months after surgery, and these individuals often have poor overall survival. Objectives: This study aims to clarify the application value of serial circulating tumor DNA (ctDNA) analysis in predicting the clinical outcome of IU-CRLM patients following liver metastasectomy. Design: A retrospective study was conducted on a cohort of patients with IU-CRLM between February 2018 and April 2021. Methods: Plasma samples at different time points during CRLM treatment [baseline (BL), preoperation (PRE), postoperation (POST), end-of-treatment (EOT), and progressive disease (PD)] were retrospectively collected from patients with initially unresectable CRLM enrolled at the Sun Yat-sen University Cancer Center. Dynamic changes of SEPTIN 9 (SEPT9) and Neuropeptide Y (NPY) methylated circulating tumor DNA (MetctDNA) levels in serial plasma samples were detected using droplet-digital PCR (ddPCR). Results: SEPT9 and NPY genes were hypermethylated in colon cancer cell lines and tissues while no difference was observed between primary and metastatic tumors. Patients with MetctDNA positive at POST or EOT had significantly lower recurrence-free survival (RFS) compared to patients with MetctDNA negative at these time points [POST: Hazard ratio (HR) 9.44, 95% confidence interval (CI) 5.15-17.30, p < 0.001; EOT: HR 11.48, 95% CI 3.27-40.31, p < 0.001]. Multivariate analysis demonstrated that POST (OR 33.96, 95% CI 4.03-286.10, p = 0.001) and EOT (OR 18.36, 95% CI 1.14-295.71, p = 0.04) MetctDNA was an independent risk factor for early recurrence. Time-dependent receiver operating characteristic curve (T-ROC) analysis revealed that area under the curve (AUC) value was greatest at the relapse time point of 6 months post-intervention, with POST-AUC and EOT-AUC values of 0.74 (95% CI 0.66-0.81) and 0.73 (95% CI 0.53-0.94), respectively. Serial MetctDNA analysis showed that RFS was significantly lower in patients with no MetctDNA clearance compared with those with MetctDNA clearance (HR 26.05, 95% CI 4.92-137.81, p < 0.001). Conclusion: Our study confirmed that serial ctDNA analysis of NPY and SEPT9 gene methylation could effectively predict early recurrence in IU-CRLM patients, especially at POST and EOT.
RESUMO
Avermectin (AVM) is presently one of the most extensively employed insecticides across the globe. A number of toxicity research studies of AVM have been carried out in freshwater-farmed carp; however, there are currently no toxicity studies on the liver. This investigation aims to replicate an acute liver injury model induced by AVM in carp, subsequently analyzing the adverse effects imposed on the nontarget species while delving into potential mechanisms underlying its toxicity. In this study, we found that AVM-exposed carp liver tissue showed cellular hydration degeneration and necrosis and reduced the viability of hepatocyte L8824. Second, AVM induced oxidative stress in carp, and AVM stimulation led to reactive oxygen species (ROS) accumulation and Ca2+ overload in hepatocyte L8824, suggesting that AVM exposure induces mitochondrial dysfunction in hepatocytes. AVM induced inflammation in carp liver tissue by inducing mitochondrial kinetic disruption, which triggered hepatic tissue injury. AVM induced autophagy and apoptosis in carp liver tissue and ROS mediated AVM-induced autophagy and apoptosis. The formation of autophagy attenuated the AVM-induced liver injury. In conclusion, the present study elucidated the hepatotoxicity and potential mechanisms of freshwater aquaculture carp exposed to the pesticide AVM, emphasized the importance of monitoring pesticide AVM contamination in freshwater aquaculture aquatic environments, and provided theoretical references for the targeted prevention of AVM-induced toxicity in carp.
Assuntos
Carpas , Doença Hepática Induzida por Substâncias e Drogas , Praguicidas , Animais , Espécies Reativas de Oxigênio , Praguicidas/toxicidade , Hepatócitos , Estresse Oxidativo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , ApoptoseRESUMO
Background: Gastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients. Methods: We studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature's performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model. Results: There were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model. Conclusion: In conclusion, we discovered a 6 gene signature to forecast GC patients' OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice.
RESUMO
Immunogenic cell death (ICD) has been increasingly indicated to be related to caners. However, ICD's role in Lung adenocarcinoma (LUAD) is still not well investigated. Clinical data along with associated mRNA expression profiles from LUAD cases were collected in TCGA and GEO databases. 13 ICD-related genes were identified. Relations of ICD-related genes expression with prognosis of patients, tumor immune microenvironment (TIME) was analyzed. Then, candidate genes were identified and the prognostic signature were constructed. Afterwards, one nomogram incorporating those chosen clinical data together with risk scores were built. Finally, the effect of HSP90AA1, one gene of the prognostic signature, on LUAD cell were analyzed. Two clusters were identified, which were designated as the ICD-high or -low subtype according to ICD-related genes levels. ICD-high subgroup showed good prognosis, high immune cell infiltration degrees, and enhanced immune response signaling activity compared with ICD-low subtype. Moreover, we established and verified the risk signature based on ICD-related genes. High risk group predicted poor prognosis of LUAD independently and presented negative association with immune score and immune status. Furthermore, nomogram contributed to the accurate prediction of LUAD prognostic outcome. Finally, HSP90AA1 levels were remarkably elevated within tumor cells in comparison with healthy pulmonary epithelial cells. HSP90α, HSP90AA1 protein product, promoted growth, migration, and invasion of LUAD cells. Molecular subtypes and prognostic model were identified by incorporating ICD-related genes, and it was related to TIME and might be adopted for the accurate prediction of LUAD prognosis.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Morte Celular Imunogênica , Adenocarcinoma de Pulmão/genética , Células Epiteliais , Neoplasias Pulmonares/genética , Microambiente Tumoral/genéticaRESUMO
Urban space architectural color is the first feature to be perceived in a complex vision beyond shape, texture and material, and plays an important role in the expression of urban territory, humanity and style. However, because of the difficulty of color measurement, the study of architectural color in street space has been difficult to achieve large-scale and fine development. The measurement of architectural color in urban space has received attention from many disciplines. With the development and promotion of information technology, the maturity of street view big data and deep learning technology has provided ideas for the research of street architectural color measurement. Based on this background, this study explores a highly efficient and large-scale method for determining architectural colors in urban space based on deep learning technology and street view big data, with street space architectural colors as the research object. We conducted empirical research in Jiefang North Road, Tianjin. We introduced the SegNet deep learning algorithm to semantically segment the street view images, extract the architectural elements and optimize the edges of the architecture. Based on K-Means clustering model, we identified the colors of the architectural elements in the street view. The accuracy of the building color measurement results was cross-sectionally verified by means of a questionnaire survey. The validation results show that the method is feasible for the study of architectural colors in street space. Finally, the overall coordination, sequence continuity, and primary and secondary hierarchy of architectural colors of Jiefang North Road in Tianjin were analyzed. The results show that the measurement model can realize the intuitive expression of architectural color information, and also can assist designers in the analysis of architectural color in street space with the guidance of color characteristics. The method helps managers, planners and even the general public to summarize the characteristics of color and dig out problems, and is of great significance in the assessment and transformation of the color quality of the street space environment.