RESUMO
The evolution of insect resistance to insecticides is frequently associated with overexpression of one or more cytochrome P450 enzyme genes. Although overexpression of CYP450 genes is a well-known mechanism of insecticide resistance, the underlying regulatory mechanisms are poorly understood. Here we uncovered the mechanisms of overexpression of the P450 gene, CYP321A8 in a major pest insect, Spodoptera exigua that is resistant to multiple insecticides. CYP321A8 confers resistance to organophosphate (chlorpyrifos) and pyrethroid (cypermethrin and deltamethrin) insecticides in this insect. Constitutive upregulation of transcription factors CncC/Maf are partially responsible for upregulated expression of CYP321A8 in the resistant strain. Reporter gene assays and site-directed mutagenesis analyses demonstrated that CncC/Maf enhanced the expression of CYP321A8 by binding to specific sites in the promoter. Additional cis-regulatory elements resulting from a mutation in the CYP321A8 promoter in the resistant strain facilitates the binding of the orphan nuclear receptor, Knirps, and enhances the promoter activity. These results demonstrate that two independent mechanisms; overexpression of transcription factors and mutations in the promoter region resulting in a new cis-regulatory element that facilitates binding of the orphan nuclear receptor are involved in overexpression of CYP321A8 in insecticide-resistant S. exigua.
Assuntos
Resistência a Inseticidas/genética , Inseticidas/farmacologia , Sequências Reguladoras de Ácido Nucleico , Spodoptera/efeitos dos fármacos , Spodoptera/genética , Animais , Sequência de Bases , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica , Proteínas de Insetos/genética , Mutação , Regiões Promotoras GenéticasRESUMO
Environmental arsenic exposure is one of the major global public health problems. Studies have shown that arsenic exposure can cause renal fibrosis, but the underlying mechanism is still unclear. Integrating the in vivo and in vitro models, this study investigated the potential molecular pathways for arsenic-induced renal fibrosis. In this study, SD rats were treated with 0, 5, 25, 50, and 100 mg/L NaAsO2 for 8 weeks via drinking water, and HK2 cells were treated with different doses of NaAsO2 for 48 h. The in vivo results showed that arsenic content in the rats' kidneys increased as the dose increased. Body weight decreased and kidney coefficient increased at 100 mg/L. As a response to the elevated NaAsO2 dose, inflammatory cell infiltration, renal tubular injury, glomerular atrophy, tubulointerstitial hemorrhage, and fibrosis became more obvious indicated by HE and Masson staining. The kidney transcriptome profiles further supported the protein-protein interactions involved in NaAsO2-induced renal fibrosis. The in vivo results, in together with the in vitro experiments, have revealed that exposure to NaAsO2 disturbed mitochondrial dynamics, promoted mitophagy, activated inflammation and the TGF-ß1/SMAD signaling pathway, and finally resulted in fibrosis. In summary, arsenic exposure contributed to renal fibrosis via regulating the mitochondrial dynamics and the NLRP3-TGF-ß1/SMAD signaling axis. This study presented an adverse outcome pathway for the development of renal fibrosis due to arsenic exposure through drinking water.
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Arsênio , Rim , Dinâmica Mitocondrial , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Arsênio/toxicidade , Linhagem Celular , Fibrose/induzido quimicamente , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Dinâmica Mitocondrial/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
In this study, daily average PM2.5 forecasting models were developed and applied in the Northern Xinjiang, China, through combining the back propagation artificial neural network (BPANN) and multiple linear regression (MLR) with another BPANN model. The meteorological (daily average precipitation, pressure, relative humidity, temperature, and wind speed, daily maximum wind speed and sunshine hours on the same day) and air pollutant data (daily PM2.5, PM10, SO2, CO, NO2, and O3 concentrations on the previous day) in January and August of each year from 2015 to 2019 were used as candidate inputs. The optimal member and combining models were evaluated through the leave-one-out cross-validation (LOOCV), fivefold cross-validation, and hold-out methods. Twelve member models with optimal or sub-optimal performance were further used to develop the combining models. The performances of the BPANN and MLR member models were different using three data division methods. The models were evaluated more comprehensively through the LOOCV. The performances of the combining models were generally better than the member models. For both member and combining models, the PM2.5 forecasting model performance in August was generally better than in January. The correlation coefficient (R) for the validation set of the optimal combination model was about 0.87 in January and 0.946 in August. These results showed that combining linear and nonlinear models through multiple data division methods would be an effective tool to forecast PM2.5 concentrations.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Previsões , Aprendizado de Máquina , Material Particulado/análiseRESUMO
Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in detoxification of electrophilic toxic compounds. Although the co-induced expression of GST genes by insecticides in insects has been documented in recent years, the underlying regulatory mechanisms are not understood. In this study, a total of thirty-one cytosolic S. exigua GSTs (SeGSTs) was cloned and identified. The bioinformatics and gene expression patterns were also analyzed. Out of them, SeGSTe9, SeGSTs6, SeGSTe1, SeGSTe6, SeGSTe8, SeGSTe14, and SeGSTd1 were significantly co-expressed following exposure to three insecticides (lambda-cyhalothrin, chlorpyrifos and chlorantraniliprole). The analysis of upstream sequences revealed that all of these seven SeGSTs harbored CncC/Maf binding site. The luciferase reporter assay showed that the pGL3-SeGST promoter construct exhibited a significant increase in luciferase activities after exposure to insecticides, and mutation of CncC/Maf binding site diminish the induction effect. These data indicate that CncC/Maf pathway regulates the co-expression of GST genes in response to different insecticides in S. exigua. Insecticides significantly enhanced the ROS content and treatment with the ROS inhibitor N-acetylcysteine (NAC) decreased the insecticide-induced luciferase activities of the PGL3-GSTe6 promoter construct, but not the CncC-mutated construct. These results indicate that ROS mediates GST gene expression after exposure to insecticides through CncC/Maf pathway. Overall, these data show that insecticides induce the co-expression of glutathione S-transferases through the ROS/CncC pathway in S. exigua.
Assuntos
Glutationa Transferase/metabolismo , Inseticidas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Spodoptera/efeitos dos fármacos , Spodoptera/metabolismo , Animais , Glutationa Transferase/genética , Proteínas de Insetos/genética , Resistência a Inseticidas/genéticaRESUMO
BACKGROUND/AIMS: The diagnosis of type 2 diabetic nephropathy (T2DN) patients is important to prevent the long-term damaging effects of kidney loss in patients with diabetes and is decisive for patient outcomes. The aim of this study was to explore urine retinol binding protein (RBP) and neutrophil gelatinase-associated lipocalin (NGAL) in T2DN patients with and without albuminuria. METHODS: A total of 293 T2DN patients were divided into three groups according to their urine albumin/urine creatinine ratio (UACR): normoalbuminuria group (UACR<30 mg/g, n=100), microalbuminuria group (UACR 30-300 mg/g, n=100) and macroalbuminuria group (UACR>300 mg/g, n=93); 50 non-diabetic subjects were recruited as the control group. The levels of urine RBP, NGAL, TNF-α and IL-18 in T2DN patients and non-diabetic subjects were measured using ELISA assays. RESULTS: We first analyzed the clinical characteristics of the control and T2DN groups and found that urine NGAL, RBP, TNF-α and IL-18 levels were significantly increased and significantly correlated with the degree of albuminuria. In addition, univariate linear regression analysis showed that urine RBP was associated with UACR, BMI, Scr, BUN, TG, disease duration, SBP, NGAL, TNF-α and IL-18 levels, and urine NGAL was positively correlated with UACR, Scr, BUN, RBP, TNF-α and IL-18 levels. CONCLUSION: The results indicate that urine levels of NGAL and RBP may be independently associated with albuminuria in T2DN and may serve as novel biomarkers for the identification of T2DN.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/urina , Lipocalina-2/urina , Proteínas de Ligação ao Retinol/urina , Idoso , Idoso de 80 Anos ou mais , Albuminúria/complicações , Albuminúria/urina , Biomarcadores/urina , Nefropatias Diabéticas/diagnóstico , Feminino , Humanos , Interleucina-18/urina , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/urinaRESUMO
Carbon black nanoparticles (CBNPs) are widely distributed in the environment and are increasingly recognized as a contributor in the development of cardiovascular disease. A variety of cardiac injuries and diseases result from structural and functional damage to cardiomyocytes. This study explored the mechanisms of CBNPs-mediated myocardial toxicity. CBNPs were given to mice through intra-tracheal instillation and it was demonstrated that the particles can be taken up into the cardiac tissue. Exposure to CBNPs induced cardiomyocyte inflammation and apoptosis. In combination with in vitro experiments, we showed that CBNPs increased the ROS and induced mitochondria fragmentation. Functionally, CBNPs-exposed cardiomyocyte exhibited depolarization of the mitochondrial membrane potential, release of cytochrome c, and activation of pro-apoptotic BAX, thereby initiating programmed cell death. On the other hand, CBNPs impaired autophagy, leading to the inadequate removal of dysfunctional mitochondria. The excess accumulation of damaged mitochondria further stimulated NF-κB activation and triggered the NLRP3 inflammasome pathway. Both the antioxidant N-acetylcysteine and the autophagy activator rapamycin were effective to attenuate the damage of CBNPs on cardiomyocytes. Taken together, this study elucidated the potential mechanism underlying CBNPs-induced myocardial injury and provided a scientific reference for the evaluation and prevention of the CBNPs-related heart risk.
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Apoptose , Autofagia , Potencial da Membrana Mitocondrial , Dinâmica Mitocondrial , Miócitos Cardíacos , Nanopartículas , Espécies Reativas de Oxigênio , Fuligem , Animais , Fuligem/toxicidade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Espécies Reativas de Oxigênio/metabolismo , Autofagia/efeitos dos fármacos , Camundongos , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Inflamassomos/metabolismo , NF-kappa B/metabolismo , NF-kappa B/genética , Acetilcisteína/farmacologia , Masculino , Sirolimo/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Melanoma is a prevalent malignant skin tumor known for its high invasive ability and a high rate of metastasis, making clinical treatment exceptionally challenging. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and play a crucial role in tumor survival and development. Cold atmospheric plasma (CAP) is an emerging tool for tumor treatment that has garnered attention from scholars due to its interaction with non-tumor cells in the tumor microenvironment. Here, we used the macrophage lines THP-1 and RAW264.7, as well as the melanoma cell lines A375 and MV3, as research subjects to investigate the effect of plasma-activated liquid (PAL) on macrophage differentiation and its inhibitory effect on melanoma cell proliferation. We confirmed that the killing effect of PAL on melanoma cells was selective. Using flow cytometry and PCR, we discovered that PAL can influence macrophage differentiation. Through in vitro cell coculture, we demonstrated that PAL-treated macrophages can significantly impede tumor cell development and progression, and the effect is more potent than that of PAL directly targeting tumor cells. Furthermore, we have proposed the hypothesis that PAL promotes the differentiation of macrophages into the M1 type through the ROS/JAK2/STAT1 pathway. To test the hypothesis, we employed catalase and fludarabine to block different sites of the pathway. The results were then validated through Western Blot, qPCR and ELISA. This study illustrates that PAL therapy is an effective tumor immunotherapy and expands the scope of tumor immunotherapy. Furthermore, these findings establish a theoretical foundation for potential clinical applications of PAL.
Assuntos
Janus Quinase 2 , Macrófagos , Melanoma , Gases em Plasma , Espécies Reativas de Oxigênio , Fator de Transcrição STAT1 , Transdução de Sinais , Janus Quinase 2/metabolismo , Fator de Transcrição STAT1/metabolismo , Gases em Plasma/farmacologia , Humanos , Melanoma/patologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células RAW 264.7 , Diferenciação Celular/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Células THP-1 , Microambiente Tumoral/efeitos dos fármacosRESUMO
Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses. Chinese Clinical Trial Registry (ChiCTR2300069993).
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Arsenic containment is one of the most severe environmental problems. It has been reported that arsenic exposure could cause male reproductive damage. However, the evidence chain from sodium arsenite (NaAsO2) exposure to adverse male fertility outcomes has not been completed by molecular events. In this study, adult male rats were exposed to NaAsO2 for eight weeks via drinking water for verifying their reproductive capacity by checking the phenotypes of testis damage, sperm quality, and female pregnancy rate. H&E staining indicated testicular cells had atrophied, and necrosis was observed under transmission electron microscopy. Sperm viability tended to decrease, and sperm malformation increased. Notably, metabolites in the testes and sperm showed substantial disruption, especially sperm metabolites. The pregnancy rate tests showed that arsenic decreased male rats' reproduction, with some adverse outcomes of the increased numbers of unpregnant females. However, the fetal crown-rump length remained unaltered, indicating that the pregnancy rate was impacted by arsenic exposure but not fetal growth. On arsenic toxicometabolomics analysis, docosahexaenoic acid (DHA) in sperm was the clearest metabolic sign to correlate with the unpregnant rate. In summary, arsenic exposure can cause male infertility via the injured sperm, which results in decreased female pregnancy. The DHA information may imply the dietary intervention for improving sperm quality. Although the fetal growth of the successful pregnancy has not been affected, the changes in epigenetic phenotypes carried by sperms still need to be verified.
Assuntos
Arsênio , Infertilidade Masculina , Gravidez , Humanos , Ratos , Masculino , Feminino , Animais , Testículo/metabolismo , Arsênio/toxicidade , Arsênio/metabolismo , Contagem de Espermatozoides , Sêmen , Ratos Sprague-Dawley , Espermatozoides , Infertilidade Masculina/induzido quimicamenteRESUMO
Objectives: This study aimed to analyze the predictive value of umbilical cord blood Interleukin-6 (UCB IL-6) for the severity-graded BPD and to establish machine learning (ML) predictive models in a Chinese population based on the 2019 NRN evidence-based guidelines. Methods: In this retrospective analysis, we included infants born with gestational age <32 weeks, who underwent UCB IL-6 testing within 24â h of admission to our NICU between 2020 and 2022. We collected their medical information encompassing the maternal, perinatal, and early neonatal phases. Furthermore, we classified the grade of BPD according to the 2019 NRN evidence-based guidelines. The correlation between UCB IL-6 and the grades of BPD was analyzed. Univariate analysis and ordinal logistic regression were employed to identify risk factors, followed by the development of ML predictive models based on XGBoost, CatBoost, LightGBM, and Random Forest. The AUROC was used to evaluate the diagnostic value of each model. Besides, we generated feature importance distribution plots based on SHAP values to emphasize the significance of UCB IL-6 in the models. Results: The study ultimately enrolled 414 preterm infants, with No BPD group (n = 309), Grade 1 BPD group (n = 73), and Grade 2-3 BPD group (n = 32). The levels of UCB IL-6 increased with the grades of BPD. UCB IL-6 demonstrated clinical significance in predicting various grades of BPD, particularly in distinguishing Grade 2-3 BPD patients, with an AUROC of 0.815 (95% CI: 0.753-0.877). All four ML models, XGBoost, CatBoost, LightGBM, and Random Forest, exhibited Micro-average AUROC values of 0.841, 0.870, 0.851, and 0.878, respectively. Notably, UCB IL-6 consistently appeared as the most prominent feature across the feature importance distribution plots in all four models. Conclusion: UCB IL-6 significantly contributes to predicting severity-graded BPD, especially in grade 2-3 BPD. Through the development of four ML predictive models, we highlighted UCB IL-6's importance.
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Milk thistle is a traditional medicinal herb. Silybin is a medicinal component found in the seed coat of milk thistle, which has liver-protective and anti-cancer properties. Conventional studies have focused on the extraction of silybin with organic reagents, which was inapplicable to the food industry. This study aims to develop a fermented milk containing silybin and protein from the milk thistle seeds. A three step procedure was developed, comprising homogenization of milk thistle seeds, NaHCO3 heat treatment, and microbial fermentation. The silybin was characterized by high performance liquid chromatography, and the protein was quantified and electrophorized. It was found that the homogenization step was essential for the preparation of protein, and the NaHCO3 heat treatment was the crucial step in obtaining silybin. The optimal NaHCO3 treatment settings were 1% NaHCO3, 60°C, and 3 h, and the optimal strains for microbial fermentation were L131 (Rummeliibacillus stabekisii) and RS72 (Lactobacillus plantarum). The silybin yield in the fermented milk reached 11.24-12.14 mg/g seeds, accounting for 72.6-78.4% of the total silybin in the milk thistle seeds, and the protein yield reached 121.8-129.6 mg/g seeds. The fermented milk had a slightly sweet yoghurt-like flavor and could be used as a dietary supplement for silybin and protein.
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Biowaste treatment by black soldier fly larvae (BSFL, Hermetia illucens) has received global research interest and growing industrial application. Larvae farming conditions, such as temperature, pH, and moisture, have been critically examined. However, the substrate carbon to nitrogen ratio (C/N), one of the key parameters that may affect larval survival and bioconversion efficiency, is significantly less studied. The current study aimed to compare the nitrogen supplying effects of 9 nitrogen species (i.e., NH4Cl, NaNO3, urea, uric acid, Gly, L-Glu, L-Glu:L-Asp (1:1, w/w), soybean flour, and fish meal) during food waste larval treatment, and further examine the C/N effects on the larval development and bioconversion process, using the C/N adjustment with urea from the initial 21:1 to 18:1, 16:1, 14:1, 12:1, and 10:1, respectively. The food wastes were supplied with the same amount of nitrogen element (1 g N/100 g dry wt) in the nitrogen source trial and different amount of urea in the C/N adjustment trial following larvae treatment. The results showed that NH4Cl and NaNO3 caused significant harmful impacts on the larval survival and bioconversion process, while the 7 organic nitrogen species resulted in no significant negative effect. Further adjustment of C/N with urea showed that the C/N range between 18:1 and 14:1 was optimal for a high waste reduction performance (73.5-84.8%, p < 0.001) and a high larvae yield (25.3-26.6%, p = 0.015), while the C/N range of 18:1 to 16:1 was further optimal for an efficient larval protein yield (10.1-11.1%, p = 0.003) and lipid yield (7.6-8.1%, p = 0.002). The adjustment of C/N influenced the activity of antioxidant enzymes, such as superoxide dismutase (SOD, p = 0.015), whereas exerted no obvious impact on the larval amino acid composition. Altogether, organic nitrogen is more suitable than NH4Cl and NaNO3 as the nitrogen amendment during larval food waste treatment, addition of small amounts of urea, targeting C/N of 18:1-14:1, would improve the waste reduction performance, and application of C/N at 18:1-16:1 would facilitate the larval protein and lipid bioconversion process.
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Toxicological data demonstrate that nanoplastics (NPs) can cause direct adverse health effects. However, a method for quantifying NPs in biological samples is lacking to date. In this study, a diatomite associated coagulation-sedimentation extraction (CSE) protocol was developed to selectively enrich polystyrene nanoplastics (PS-NP) from microplastics (PS-MP) in the digest of animal tissues, which were then analyzed using pyrolysis gas chromatography-mass spectrometry. We demonstrate that 0.02 g of 7-µm diatomite can selectively adsorb 70-nm PS-NP in 5 mL oyster digest. The method works in the range of 0.006-5 µg PS-NP per 0.5 g wet weight tissue, which has been verified via samples of environmentally contaminated oysters and chow diet PS-NP-treated C57BL/6 mice (digestive tract, kidney, and liver tissues). The particle size-dependent colloidization or buoyancy theoretically supported the general CSE procedure. This work will pave the way for assessing human exposure to NPs and associated health risks.
Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microplásticos , Plásticos , Poliestirenos/análise , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Glutathione S-transferases (GSTs) are a superfamily of multifunctional dimeric proteins existing in both prokaryotic and eukaryotic organisms. They are involved in the detoxification of both endogenous and exogenous electrophiles, including insecticides. However, the molecular mechanisms underlying the regulation of GST genes in insects are poorly understood. RESULTS: We first identified at least three GST genes involved in resistance to the insecticides chlorpyrifos and cypermethrin. Analysis of upstream sequences revealed that three GSTs (SeGSTo2, SeGSTe6 and SeGSTd3) harbor the same cap 'n' collar C/muscle aponeurosis fibromatosis (CncC/Maf) binding site, and SeGSTo2 and SeGSTe6 contain the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) binding site. Luciferase reporter assay showed co-transfection of reporter plasmid containing the SeGSTe6 promoter with CncC and/or Maf expressing constructs significantly boosted transcription. Similarly, AhR and/or ARNT expressing constructs also significantly increased the promoter activities. The co-transfection of mutated reporter plasmid with CncC/Maf or AhR/ARNT did not increase transcription activity anymore. Constitutive over-expression of CncC, Maf and AhR was also found in the HZ16 strain, which might be the molecular mechanism for up-regulated expression of multiple detoxification genes conferring resistance to insecticides. CONCLUSION: These results suggest that CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GST genes involved in insecticide resistance in Spodoptera exigua. © 2019 Society of Chemical Industry.
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Clorpirifos/farmacocinética , Glutationa Transferase/metabolismo , Resistência a Inseticidas/genética , Piretrinas/farmacologia , Spodoptera/efeitos dos fármacos , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto , Sítios de Ligação , Glutationa Transferase/genética , Inativação Metabólica , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inseticidas/farmacologia , Regiões Promotoras Genéticas , Spodoptera/genética , Spodoptera/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Cytochrome P450 and UDP-glucosyltransferase (UGT) as phase I and phase II metabolism enzymes, respectively, play vital roles in the breakdown of endobiotics and xenobiotics. Insects can increase the expression of detoxification enzymes to cope with the stress from xenobiotics including insecticides. However, the molecular mechanisms for insecticide detoxification in Spodoptera exigua remain elusive, and the genes conferring insecticide metabolisms in this species are less well reported. In this study, 68 P450 and 32 UGT genes were identified. Phylogenetic analysis showed gene expansions in CYP3 and CYP4 clans of P450 genes and UGT33 family of this pest. P450 and UGT genes exhibited specific tissue expression patterns. Insecticide treatments in fat body cells of S. exigua revealed that the expression levels of P450 and UGT genes were significantly influenced by challenges of abamectin, lambda-cyhalothrin, chlorantraniliprole, metaflumizone and indoxacarb. Multiple genes for detoxification were affected in expression levels after insecticide exposures. The results demonstrated that lambda-cyhalothrin, chlorantraniliprole, metaflumizone and indoxacarb induced similar responses in the expression of P450 and UGT genes in fat body cells; eight P450 genes and four UGT genes were co-up-regulated significantly, and no or only a few CYP/UGT genes were down-regulated significantly by these four insecticides. However, abamectin triggered a distinct response for P450 and UGT gene expression; more P450 and UGT genes were down-regulated by abamectin than by the other four compounds. In conclusion, P450 and UGT genes from S. exigua were identified, and different responses to abamectin suggest a different mechanism for insecticide detoxification.
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Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Inseticidas , Spodoptera/efeitos dos fármacos , Animais , Expressão Gênica , Filogenia , Spodoptera/genética , Spodoptera/metabolismoRESUMO
Flonicamid is a selective insecticide for the control of sap-sucking insects; it exerts toxic effects by inhibiting insect feeding. However, its molecular target remains elusive. In this study, we functionally characterized NlKir1 channels of the brown planthopper (Nilaparvata lugens) in HEK293â¯cells. Homomeric NlKir1 channels generated inward-rectifying K+ currents. Flonicamid inhibited NlKir1 channels at nanomolar concentrations. Furthermore, flonicamid inhibited honeydew and salivary secretions of planthoppers, and reduced the renal excretion of female mosquitoes in a dose-dependent manner. The inhibitory effect of flonicamid on fluid secretion of isolated Malpighian tubules from Culex pipiens pullens was comparable to that of the selective Kir1 inhibitor. The observed physiological alterations by flonicamid are likely mediated by Kir1 channels and could lead to the disruption of feeding behaviors and eventually lethality. Our study establishes the Kir1 channel as the target of flonicamid and provided new insights into the mode of action of flonicamid.
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Besouros/metabolismo , Culex/metabolismo , Hemípteros/metabolismo , Proteínas de Insetos/antagonistas & inibidores , Túbulos de Malpighi/metabolismo , Niacinamida/análogos & derivados , Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores , Glândulas Salivares/metabolismo , Animais , Proteínas de Insetos/metabolismo , Niacinamida/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismoRESUMO
PURPOSE: Tacrolimus is an effective (but relatively expensive) immunosuppressant that is used widely in patients with membranous nephropathy. To reduce the tacrolimus dose while maintaining an equivalent therapeutic effect, we studied the clinical efficacy and pharmacoeconomic impact of co-administration of Wuzhi capsules (WZC that protects against damage to liver cells) and tacrolimus. METHODS: Sixty patients with membranous nephropathy were divided randomly into two groups: experimental (tacrolimus + WZC + corticosteroids) and control (tacrolimus + corticosteroids). Each group received treatments continuously for >6 months. Liver function; renal function; and whole-blood concentrations of tacrolimus, sugars, lipids, as well as 24-h urinary protein levels were used in the clinical evaluation. The cost of drugs was calculated, and the pharmacoeconomic cost-effectiveness analyses were carried out to compare indices between the two groups. RESULTS: Doses and costs of tacrolimus differed significantly between experimental and control groups (p < 0.01 or p < 0.05). Costs in the experimental group were 13,702.62 ± 1,458.6 CNY (2,194.10 ± 233.56 USD) and those in the control group were 17,796.87 ± 2,469.27 CNY (2,849.69 ± 395.39 USD), with clinical efficacy of 93.3 and 90.0 %, respectively. The cost-effectiveness ratios were 146.86 ± 15.63 and 197.73 ± 27.44, respectively. Compared with the experimental group, the control group showed an incremental cost-effectiveness ratio of 1,240.68 ± 306.25 CNY (198.66 ± 49.04 USD), whereas remission between the two groups was similar. CONCLUSION: Co-administration of WZCs and tacrolimus can reduce the dose of tacrolimus and decrease the costs incurred by patients within the same therapeutic window to that seen for treatment with tacrolimus alone.
Assuntos
Medicamentos de Ervas Chinesas/economia , Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/economia , Imunossupressores/uso terapêutico , Tacrolimo/economia , Tacrolimo/uso terapêutico , Corticosteroides/economia , Corticosteroides/uso terapêutico , Adulto , Biópsia , Cápsulas , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/farmacocinética , Farmacoeconomia , Feminino , Humanos , Imunossupressores/farmacocinética , Testes de Função Renal , Testes de Função Hepática , Masculino , Tacrolimo/farmacocinética , Resultado do TratamentoRESUMO
Feasibility of bioleaching combining with Fenton-like reaction to remove heavy metals from sewage sludge was investigated. After 5-day bioleaching, the sludge pH decreased from 6.95 to 2.50, which satisfied the acidic conditions for Fenton-like reaction. Meanwhile, more than 50% of sludge-borne heavy metals were dissolved except for Pb. The bioleached sludge was further oxidized with Fenton-like reaction, with an optimal H2O2 dosage of 5 g/L, the Cu, Zn, Pb and Cd removal reached up to 75.3%, 72.6%, 34.5% and 65.4%, respectively, and the residual content of heavy metals in treated sludge meets the requirement of Disposal of Sludge from Municipal Wastewater Treatment Plant - Control Standards for Agricultural Use (CJ/T 309-2009) of China for A grade sludge. Bioleaching combined with Fenton-like reaction was the most effective method for heavy metal removal, compared with 15-day bioleaching and inorganic acid leaching with 10% H2SO4, 10% HCl and 10% HNO3.
Assuntos
Metais Pesados/isolamento & purificação , Esgotos/química , Estudos de Viabilidade , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , SolubilidadeRESUMO
Graphene, as an ideal two-dimensional material and single-atom layer of graphite, has attracted exploding interests in multidisciplinary research because of its unique structure and exceptional physicochemical properties. Especially, graphene-based materials offer a wide range of potentialities for environmental remediation and energy applications. This review shows an extensive overview of the main principles and the recent synthetic technologies about designing and fabricating various innovative graphene-based materials. Furthermore, an extensive list of graphene-based sorbents and catalysts from vast literature has been compiled. The adsorptive and catalytic properties of graphene-based materials for the removal of various pollutants and hydrogen storage/production as available in the literature are presented. Tremendous adsorption capacity, excellent catalytic performance and abundant availability are the significant factors making these materials suitable alternatives for environmental pollutant control and energy-related system, especially in terms of the removal of pollutants in water, gas cleanup and purification, and hydrogen generation and storage. Meanwhile, a brief discussion is also included on the influence of graphene materials on the environment, and its toxicological effects. Lastly, some unsolved subjects together with major challenges in this germinating area of research are highlighted and discussed. Conclusively, the expanding of graphene-based materials in the field of adsorption and catalysis science represents a viable and powerful tool, resulting in the superior improvement of environmental pollution control and energy development.