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1.
RSC Adv ; 14(37): 27132-27140, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39193290

RESUMO

Hydrogen production via cost-effective electrochemical water splitting is one of the most promising approaches to confront the energy crisis and to obtain clean fuels with high energy density. To address this concern, herein, we developed a simple one-step synthesis method for creating an AuAgCu trimetallic alloy using aspirin as a capping agent. This alloy shows potential for efficient electrocatalyst for hydrogen evolution reaction. The trimetallic nanoparticles based alloy exhibit an equiaxed grain-like morphology and a face-centred cubic phase. In HER experiments using a 1 M KOH electrolyte, the AuAgCu alloy shows nearly negligible overpotential compared to mono- and bimetallic catalysts, and the Tafel slope was 32.7 mV dec-1, which is the lowest ever achieved for alloy-based electrocatalysts and extremely close to a commercially available Pt/C with high stability for 21 days and no decrease in current density in alkaline media. Besides, with excellent HER activity and stability, the trimetallic AuAgCu-modified electrode possessed significant durability for over 1000 cycles in the selected range of potential from 0.5 to 0.8 V at different scan rates from 1 to 100 mV s-1. This simple, cost-effective and environmentally friendly methodology can pave the way for the exploitation of mixed metal alloy-based electrocatalysts not only for water splitting but also for other applications, such as fuel cells, lithium-ion batteries and supercapacitors.

2.
Environ Res ; 262(Pt 1): 119801, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147190

RESUMO

Since the initial introduction of whole-cell bioreporters (WCBs) nearly 30 years ago, their high sensitivity, selectivity, and suitability for on-site detection have rendered them highly promising for environmental monitoring, medical diagnosis, food safety, biomanufacturing, and other fields. Especially in the environmental field, the technology provides a fast and efficient way to assess the bioavailability of pollutants in the environment. Despite these advantages, the technology has not been commercialized. This lack of commercialization is confusing, given the broad application prospects of WCBs. Over the years, numerous research papers have focused primarily on enhancing the sensitivity and selectivity of WCBs, with little attention paid to their wider commercial applications. So far, there is no a critical review has been published yet on this topic. Therefore, in this article we critically reviewed the research progress of WCBs over the past three decades, assessing the performance and limitations of current systems to understand the barriers to commercial deployment. By identifying these obstacles, this article provided researchers and industry stakeholders with deeper insights into the challenges hindering market entry and inspire further research toward overcoming these barriers, thereby facilitating the commercialization of WCBs as a promising technology for environmental monitoring.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39147447

RESUMO

Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells. We used a well-known animal model of high-fat diet-induced obesity in this investigation, and testicular dysfunction was determined by sperm DNA damage, spermatocyte chromosomal abnormalities, and spermiogram analysis. Following a 12-week high-fat diet challenge, mice were randomly assigned to dulaglutide (0.6 mg/kg/day) or saline treatments for five weeks. Testes and sperm cells were collected 24 h after the last dulaglutide injection. Untreated obese mice had a lower testes/body weight ratio, more sperm DNA damage, diakinesis-metaphase I chromosomal abnormalities, a lower sperm count/motility, more cell morphological defects, and an altered testicular redox balance. In obese mice, dulaglutide injection efficiently restored all disturbed parameters to their control levels. Dulaglutide injection into healthy mice exhibited no significant harmful effects at the applied regimen. As a result, we infer that dulaglutide therapy might bring obese men additional benefits by recovering testicular dysfunction induced by obesity.


Assuntos
Dieta Hiperlipídica , Modelos Animais de Doenças , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Obesidade , Proteínas Recombinantes de Fusão , Testículo , Animais , Masculino , Fragmentos Fc das Imunoglobulinas/farmacologia , Obesidade/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Camundongos , Proteínas Recombinantes de Fusão/farmacologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Dano ao DNA/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Aberrações Cromossômicas/efeitos dos fármacos , Doenças Testiculares/tratamento farmacológico
4.
BMC Pharmacol Toxicol ; 25(1): 56, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39175081

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses. METHODS: We focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration. RESULTS: Our computational investigation showed rivaroxaban (-4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (-5.97 kcal/mol) and dabigatran (-9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control. CONCLUSION: Overall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.


Assuntos
Arildialquilfosfatase , Fibrilação Atrial , Dabigatrana , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Piridonas , Rivaroxabana , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Arildialquilfosfatase/sangue , Rivaroxabana/uso terapêutico , Masculino , Piridonas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirazóis/química , Administração Oral , Anticoagulantes/farmacologia , Anticoagulantes/química , Feminino , Idoso , Pessoa de Meia-Idade
5.
Artigo em Inglês | MEDLINE | ID: mdl-39032854

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is marked by impaired social interactions, and increased repetitive behaviors. There is evidence of genetic changes in ASD, and several of these altered genes are linked to the process of DNA repair. Therefore, individuals with ASD must have improved DNA repair efficiency to mitigate risks associated with ASD. Despite numerous milestones in ASD research, the disease remains incurable, with a high occurrence rate and substantial financial burdens. This motivates scientists to search for new drugs to manage the disease. Disruption of glucagon-like peptide-1 (GLP-1) signaling, a regulator in neuronal development and maintains homeostasis, has been associated with the pathogenesis and progression of several neurological disorders, such as ASD. Our study aimed to assess the impact of semaglutide, a new GLP-1 analog antidiabetic medication, on behavioral phenotypes and DNA repair efficiency in the BTBR autistic mouse model. Furthermore, we elucidated the underlying mechanism(s) responsible for the ameliorative effects of semaglutide against behavioral problems and DNA repair deficiency in BTBR mice. The current results demonstrate that repeated treatment with semaglutide efficiently decreased autism-like behaviors in BTBR mice without affecting motor performance. Semaglutide also mitigated spontaneous DNA damage and enhanced DNA repair efficiency in the BTBR mice as determined by comet assay. Moreover, administering semaglutide recovered oxidant-antioxidant balance in BTBR mice. Semaglutide restored the disrupted DNA damage/repair pathways in the BTBR mice by reducing Gadd45a expression and increasing Ogg1 and Xrcc1 expression at both the mRNA and protein levels. This suggests that semaglutide holds great potential as a novel therapeutic candidate for treating ASD traits.


Assuntos
Reparo do DNA , Peptídeos Semelhantes ao Glucagon , Animais , Masculino , Peptídeos Semelhantes ao Glucagon/farmacologia , Reparo do DNA/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Comportamento Animal/efeitos dos fármacos
6.
Mol Biol Rep ; 51(1): 824, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023688

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a global life-threatening problem and therapeutic interventions are still encountered. IQGAP genes are involved in HCC oncogenesis. The modulatory effect of statins on the expression of IQGAP genes is still unclear. This study aims to study the effect of free SV and chitosan (CS) decorated simvastatin (SV) loaded solid lipid nanoparticles (C-SV-SLNs) on HCC mortality. METHODS AND RESULTS: Plain, SV-SLN, and C-SV- SLN were prepared and characterized in terms of particle size (PS), zeta potential (ZP), and polydispersity index (PDI). The biosafety of different SLN was investigated using fresh erythrocytes, moreover, cytotoxicity was investigated using HepG2 cell lines. The effect of SLNs on IQGAPs gene expression as well as JNK, HDAC6, and HDAC8 activity was investigated using PCR and MOE-docking. The current results displayed that SV-SLNs have nanosized, negative ZP and are homogenous, CS decoration shifts the ZP of SLN into cationic ZP. Furthermore, all SLNs exhibited desirable biosafety in terms of no deleterious effect on erythrocyte integrity. SV solution and SV-SLN significantly increase the mortality of HepG2 compared to undertreated cells, however, the effect of SV-SLN is more pronounced compared to free SV. Remarkably, C-SV-SLN elicits high HepG2 cell mortality compared to free SV and SV-SLN. The treatment of HepG2 cells with SV solution, SV-SLN, or C-SV-SLN significantly upregulates the IQGAP2 gene with repression of IQGAP1 and IQGAP3 genes. MOE-docking studies revealed both SV and tenivastatin exhibit interactions with the active sites of JNK, HDAC6, and HDAC8. Moreover, tenivastatin exhibited greater interactions with magnesium and zinc compared to SV. CONCLUSIONS: This research provides novel insights into the therapeutic potential of SV, SV-SLN and C-SV-SLNs in HCC treatment, modulating critical signaling cascades involving IQGAPs, JNK, and HDAC. The development of C-SV-SLNs presents a promising strategy for effective HCC therapy.


Assuntos
Carcinoma Hepatocelular , Quitosana , Histona Desacetilases , Neoplasias Hepáticas , Nanopartículas , Proteínas Ativadoras de ras GTPase , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Células Hep G2 , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Quitosana/farmacologia , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo , Nanopartículas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tamanho da Partícula , Lipossomos , Proteínas Repressoras
7.
J Hazard Mater ; 477: 135239, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39053060

RESUMO

Bisphenol-A (BPA) is an emerging hazardous contaminant, which is ubiquitous in the environment and can cause endocrine disruptor and cancer risks. Therefore, biodegradation of BPA is an essential issue to mitigate the associated human health. In this work, a bacterial strain enables of degrading BPA, named BPA-LRH8 (identified as Xenophilus sp.), was newly isolated from activated sludge and embedded onto walnut shell biochar (WSBC) to form a bio-composite (BCM) for biodegradation of BPA in water. The Langmuir maximum adsorption capacity of BPA by WSBC was 21.7 mg g-1. The free bacteria of BPA-LRH8 showed high BPA degradation rate (∼100 %) at pH 5-11, while it was lower (<20 %) at pH 3. The BCM eliminated all BPA (∼100 %) at pH 3-11 and 25-45 °C when the BPA level was ≤ 25 mg L-1. The spectrometry investigations suggested two possible degradation routes of BPA by Xenophilus sp. In one route, BPA (C15H16O3) was oxidized to C15H16O3, and then broken into C9H12O3 through chain scission. In another route, BPA was likely hydroxylated, oxidized, and cleaved into C9H10O4P4, which was further metabolized into CO2 and H2O in the TCA cycle. This study concluded that the novel isolated bacteria (BPA-LRH8) embedded onto WSBC is a promising and new method for the effective removal of BPA and similar hazardous substances from contaminated water under high concentrations and wide range of pH and temperature.


Assuntos
Compostos Benzidrílicos , Biodegradação Ambiental , Carvão Vegetal , Fenóis , Poluentes Químicos da Água , Fenóis/metabolismo , Carvão Vegetal/química , Compostos Benzidrílicos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Adsorção , Rhizobiaceae/metabolismo
8.
Sci Total Environ ; 947: 174505, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38971252

RESUMO

Nanobiotechnology is a potentially safe and sustainable strategy for both agricultural production and soil remediation, yet the potential of nanomaterials (NMs) application to remediate heavy metal(loid)-contaminated soils is still unclear. A meta-analysis with approximately 6000 observations was conducted to quantify the effects of NMs on safe crop production in soils contaminated with heavy metal(loid) (HM), and a machine learning approach was used to identify the major contributing features. Applying NMs can elevate the crop shoot (18.2 %, 15.4-21.2 %) and grain biomass (30.7 %, 26.9-34.9 %), and decrease the shoot and grain HM concentration by 31.8 % (28.9-34.5 %) and 46.8 % (43.7-49.8 %), respectively. Iron-NMs showed a greater potential to inhibit crop HM uptake compared to other types of NMs. Our result further demonstrates that NMs application substantially reduces the potential health risk of HM in crop grains by human health risk assessment. The NMs-induced reduction in HM accumulation was associated with decreasing HM bioavailability, as well as increased soil pH and organic matter. A random forest model demonstrates that soil pH and total HM concentration are the two significant features affecting shoot HM accumulation. This analysis of the literature highlights the significant potential of NMs application in promoting safe agricultural production in HM-contaminated agricultural lands.


Assuntos
Produtos Agrícolas , Metais Pesados , Poluentes do Solo , Solo , Poluentes do Solo/análise , Metais Pesados/análise , Solo/química , Produção Agrícola/métodos , Recuperação e Remediação Ambiental/métodos , Nanoestruturas , Agricultura/métodos
9.
J Biochem Mol Toxicol ; 38(7): e23764, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38963172

RESUMO

Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.


Assuntos
Dano ao DNA , Metilação de DNA , Reparo do DNA , Dieta Hiperlipídica , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Oxirredução , Proteínas Recombinantes de Fusão , Animais , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Metilação de DNA/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/farmacologia , Dano ao DNA/efeitos dos fármacos , Camundongos , Reparo do DNA/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Masculino , Oxirredução/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , Estresse Oxidativo/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos C57BL
10.
Chemosphere ; 362: 142699, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38944354

RESUMO

Predicting the parameters that influence colloidal phosphorus (CP) release from soils under different land uses is critical for managing the impact on water quality. Traditional modeling approaches, such as linear regression, may fail to represent the intricate relationships that exist between soil qualities and environmental influences. Therefore, in this study, we investigated the major determinants of CP release from different land use/types such as farmland, desert, forest soils, and rivers. The study utilizes the structural equation model (SEM), multiple linear regression (MLR), and three machine learning (ML) models (Random Forest (RF), Support Vector Regression (SVR), and eXtreme Gradient Boosting (XGBoost)) to predict the release of CP from different soils by using soil iron (Fe), aluminum (Al), calcium (Ca), pH, total organic carbon (TOC) and precipitation as independent variables. Results show that colloidal-cations (Fe, Al, Ca) and colloidal-TOC strongly influence CP release, while bioclimatic variables (precipitation) and pH have weaker effects. XGBoost outperforms the other models with an R2 of 0.94 and RMSE of 0.09. SHapley Additive Explanations described the outcomes since XGBoost is accurate. The relative relevance ranking indicated that colloidal TOC had the highest ranking in predicting CP. This was supported by the analysis of partial dependence plots, which showed that an increase in colloidal TOC increased soil CP release. According to our research, the SHAP XGBoost model provides significant information that can help determine the variables that considerably influence CP contents as compared to RF, SVM, and MLR.


Assuntos
Coloides , Aprendizado de Máquina , Fósforo , Solo , Fósforo/análise , Fósforo/química , Solo/química , Coloides/química , Poluentes do Solo/análise , Modelos Lineares , Monitoramento Ambiental/métodos , Ferro/química
11.
Sci Rep ; 14(1): 14753, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926522

RESUMO

The development of nanomaterials has been speedily established in recent years, yet nanoparticles synthesized by traditional methods suffer unacceptable toxicity and the sustainability of the procedure for synthesizing such nanoparticles is inadequate. Consequently, green biosynthesis, which employs biopolymers, is gaining attraction as an environmentally sound alternative to less sustainable approaches. Chitosan-encapsulated nanoparticles exhibit exceptional antibacterial properties, offering a wide range of uses. Chitosan, obtained from shrimp shells, aided in the environmentally friendly synthesis of high-purity zinc oxide nanoparticles (ZnO NPs) with desirable features such as the extraction yield (41%), the deacetylation (88%), and the crystallinity index (74.54%). The particle size of ZnO NPs was 12 nm, while that of chitosan-ZnO NPs was 21 nm, and the bandgap energies of these nanomaterials were 3.98 and 3.48, respectively. The strong antibacterial action was demonstrated by ZnO NPs, chitosan-ZnO NPs, and chitosan-ZnO/PVP, particularly against Gram-positive bacteria, making them appropriate for therapeutic use. The photocatalytic degradation abilities were also assessed for all nanoparticles. At a concentration of 6 × 10-5 M, chitosan removed 90.5% of the methylene blue (MB) dye, ZnO NPs removed 97.4%, chitosan-coated ZnO NPs removed 99.6%, while chitosan-ZnO/PVP removed 100%. In the case of toluidine blue (TB), at a concentration of 4 × 10-3 M, the respective efficiencies were 96.8%, 96.8%, 99.5%, and 100%, respectively. Evaluation of radical scavenger activity revealed increased scavenging of ABTS and DPPH radicals by chitosan-ZnO/PVP compared to individual zinc oxide or chitosan-ZnO, where the IC50 results were 0.059, 0.092, 0.079 mg/mL, respectively, in the ABTS test, and 0.095, 0.083, 0.061, and 0.064 mg/mL in the DPPH test, respectively. Moreover, in silico toxicity studies were conducted to predict the organ-specific toxicity through ProTox II software. The obtained results suggest the probable safety and the absence of organ-specific toxicity with all the tested samples.


Assuntos
Antibacterianos , Quitosana , Óxido de Zinco , Quitosana/química , Quitosana/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Catálise , Nanopartículas/química , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química , Compostos de Bifenilo/química , Química Verde
12.
Sci Total Environ ; 945: 173998, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38901575

RESUMO

Globally, power stations generate huge amounts of the hazardous waste heavy oil fly ash (HOFA), which is rich in Ni, V, Fe, S, and dumped into landfills. Thus, exploring new approaches for a safe recycling and sustainable management of HOFA is needed and of great environmental interest. The potential application of HOFA as an amendment to sandy soils has not been studied yet. This is the first research investigating the potentiality of using HOFA as a soil conditioner. To this end, we conducted a greenhouse experiment in order to investigate the impacts of HOFA addition (1.2, 2.4, 3.6 t ha-1) to sandy soil on the total and available content of nutrients (e.g., S, Fe, Mn, Cu, Zn) and toxic elements (TEs; e.g., Cd, Co, Cr, Ni, Pb, V) in the soil and their phytoextraction and translocation by lemongrass (Cymbopogon citratus) and common sage (Salvia officinalis). We also assessed the impact of humic acid (HA) foliar application (50 and 100 l ha-1) on the growth and elements accumulation by the two plants. The studied HOFA was acidic and highly enriched in S (43,268.0), V (3,527.0), Ni (1774.0), and Fe (15,159.0) (units in mg kg-1). The X-ray absorption near edge structure (XANES) data showed that V in HOFA was composed primarily of V(IV) sorbed onto goethite, V(V) sorbed onto humic substances, in the forms of V2O3, and VCl4. Addition of the lower doses of HOFA (1.2 and 2.4 t ha-1) did not change significantly soil pH, salinity, and the total and available elements content compared to the unamended soil. Although the elements content in the 3.6 t ha-1 HOFA-treated soil was significantly higher than the untreated, the total content of all elements (except for Ni) was lower than the maximum allowable concentrations in soils. HOFA addition, particularly in the highest dose (3.6 t ha-1), decreased significantly the growth and biomass of both plants. Common sage accumulated more elements than lemongrass; however, the elements content in the plants was lower than the critical concentrations for sensitive plants. The foliar application of humic acid enhanced significantly the plant growth and increased their tolerance to the HOFA-induced stress. We conclude that the addition of HOFA up to 2.4 t ha-1 in a single application as amendment to sandy soils is not likely to create any TE toxicity problems to plants, particularly if combined with a foliar application of humic acid; however, repeated additions of HOFA may induce toxicity. These findings should be verified under field conditions.


Assuntos
Cinza de Carvão , Substâncias Húmicas , Poluentes do Solo , Solo , Poluentes do Solo/análise , Solo/química , Cymbopogon , Fertilizantes , Enxofre , Metais Pesados/análise
13.
Eur J Med Chem ; 275: 116607, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38908102

RESUMO

Dihydropyrimidines are widely recognized for their diverse biological properties and are often synthesized by the Biginelli reactions. In this backdrop, a novel series of Biginelli dihydropyrimidines were designed, synthesized, purified, and analyzed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. Anticancer activity against MCF-7 breast cancer cells was evaluated as part of their cytotoxicity in comparison with the normal Vero cells. The cytotoxicity of dihydropyrimidines ranges from moderate to significant. Among the 38 dihydropyrimidines screened, compounds 16, 21, and 39 exhibited significant cytotoxicity. These 3 compounds were subjected to flow cytometry studies and EGFRwt Kinase inhibition assay using lapatinib as a standard. The study included evaluation for the inhibition of EGFR and HER2 expression at five different concentrations. At a concentration of 1000 nM compound 21 showed 98.51 % and 96.79 % inhibition of EGFR and HER2 expression. Moreover, compounds 16, 21 and 39 significantly inhibited EGFRwt activity with IC50 = 69.83, 37.21 and 76.79 nM, respectively. In addition, 3D-QSAR experiments were conducted to elucidate Structure activity relationships in a 3D grid space by comparing the experimental and predicted cytotoxic activities. Molecular docking studies were performed to validate the results by in silico method. All together, we developed a new series of Biginelli dihydropyrimidines as dual EGFR/HER2 inhibitors.


Assuntos
Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases , Pirimidinas , Receptor ErbB-2 , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Animais , Chlorocebus aethiops , Células MCF-7 , Relação Quantitativa Estrutura-Atividade , Células Vero , Relação Estrutura-Atividade
14.
Int Immunopharmacol ; 137: 112503, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38906008

RESUMO

Psoriasis is classified as an autoimmune disorder characterized by abnormal immune response leading to the development of chronic dermal inflammation. Most individuals have a genetic vulnerability that may be further influenced by epigenetic changes occurring due to multiple variables such as pollutant exposure. Epigenetic modifications such as DNA methylation possess a dynamic nature, enabling cellular differentiation and adaptation by controlling gene expression. Di(2-ethylhexyl) phthalate (DEHP) and psoriatic inflammation are known to cause modification of DNA methylation via DNA methyltransferase (DNMT). However, it is not known whether DEHP, a ubiquitous plasticizer affects psoriatic inflammation via DNMT modulation. Therefore, this study investigated the effect of DNMT inhibitor, 5-aza-2'-deoxycytidine (AZA) on DEHP-induced changes in the expression of DNMT1, global DNA methylation, and anti-/inflammatory parameters (p-STAT3, IL-17A, IL-6, iNOS, IL-10, Foxp3, Nrf2, HO-1) in the skin and the peripheral adaptive/ myeloid immune cells (CD4+ T cells/CD11b+ cells) in imiquimod (IMQ) model of psoriasiform inflammation. Further, psoriasis-associated clinical/histopathological features (ear thickness, ear weight, ear PASI score, MPO activity, and H&E staining of the ear and the back skin) were also analyzed in IMQ model. Our data show that IMQ-treated mice with DEHP exposure had increased DNMT1 expression and DNA methylation which was associated with elevated inflammatory (p-STAT3, IL-17A, IL-6, iNOS) and downregulated anti-inflammatory mediators (IL-10, Foxp3, Nrf2, HO-1) in the peripheral immune cells (CD4+ T cells/CD11b+ cells) and the skin as compared to IMQ-treated mice. Treatment with DNMT1 inhibitor caused reduction in inflammatory and elevation in anti-inflammatory parameters with significant improvement in clinical/histopathological symptoms in both IMQ-treated and DEHP-exposed IMQ-treated mice. In conclusion, our study shows strong evidence indicating that DNMT1 plays an important role in DEHP-induced exacerbation of psoriasiform inflammation in mice through hypermethylation of DNA.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Decitabina , Dietilexilftalato , Psoríase , Pele , Animais , Metilação de DNA/efeitos dos fármacos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/patologia , Decitabina/farmacologia , Decitabina/uso terapêutico , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Dietilexilftalato/toxicidade , Camundongos , Masculino , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Feminino
15.
Sci Total Environ ; 942: 173567, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38848918

RESUMO

The increasing trend of using agricultural wastes follows the concept of "waste to wealth" and is closely related to the themes of sustainable development goals (SDGs). Carbon-neutral technologies for waste management have not been critically reviewed yet. This paper reviews the technological trend of agricultural waste utilization, including composting, thermal conversion, and anaerobic digestion. Specifically, the effects of exogenous additives on the contents, fractionation, and fate of phosphorus (P) and potentially toxic elements (PTEs) during the composting process have been comprehensively reviewed in this article. The composting process can transform biomass-P and additive-born P into plant available forms. PTEs can be passivated during the composting process. Biochar can accelerate the passivation of PTEs in the composting process through different physiochemical interactions such as surface adsorption, precipitation, and cation exchange reactions. The addition of exogenous calcium, magnesium and phosphate in the compost can reduce the mobility of PTEs such as copper, cadmium, and zinc. Based on critical analysis, this paper recommends an eco-innovative perspective for the improvement and practical application of composting technology for the utilization of agricultural biowastes to meet the circular economy approach and achieve the SDGs.


Assuntos
Agricultura , Compostagem , Fósforo , Fósforo/análise , Agricultura/métodos , Compostagem/métodos , Gerenciamento de Resíduos/métodos
16.
J Neuroimmunol ; 391: 578365, 2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38723577

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B1 (AFB1) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB1 is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB1 results in neurological problems. The BTBR T+ Itpr3tf/J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB1 in BTBR mice. This work aimed to examine the effects of AFB1 on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19+ B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB1 exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB1 in the BTBR group exhibited a substantial increase in the presence of CD19+Notch-1+, CD19+IL-6+, CD19+MCP-1+, CD19+iNOS+, CD19+GM-CSF+, and CD19+NF-κB p65+ compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB1 to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB1 worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.


Assuntos
Aflatoxina B1 , Antígenos CD19 , Modelos Animais de Doenças , Animais , Camundongos , Aflatoxina B1/toxicidade , Antígenos CD19/metabolismo , Masculino , Mediadores da Inflamação/metabolismo , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/imunologia , Transtorno Autístico/metabolismo , Camundongos Transgênicos
17.
Artigo em Inglês | MEDLINE | ID: mdl-38821673

RESUMO

Diabetes mellitus is a complex metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors that increase the risk of cancer development. However, it is unclear whether the increased cancer risk is due to poor glycemic control or the use of some antidiabetic medications. Therefore, we investigated the genetic and epigenetic changes in somatic cells in a mouse model of diabetes and studied whether multiple exposures to the antidiabetic medication dapagliflozin influence these changes. We also elucidated the mechanism(s) of these ameliorations. The micronucleus test and modified comet assay were used to investigate bone marrow DNA damage and methylation changes. These assays revealed that dapagliflozin is non-genotoxic in the tested regimen, and oxidative DNA damage and hypermethylation were significantly higher in diabetic mice. Spectrophotometry also evaluated oxidative DNA damage and global DNA methylation, revealing similar significant alterations induced by diabetes. Conversely, the dapagliflozin-treated diabetic animals significantly reduced these changes. The expression of some genes involved in DNA repair and DNA methylation was disrupted considerably in the somatic cells of diabetic animals. In contrast, dapagliflozin treatment significantly restored these disruptions and enhanced DNA repair. The simultaneous effects of decreased oxidative DNA damage and hypermethylation levels suggest that dapagliflozin can be used as a safe antidiabetic drug to reduce DNA damage and hypermethylation in diabetes, demonstrating its usefulness in patients with diabetes to control hyperglycemia and decrease the development of its subsequent complications.


Assuntos
Compostos Benzidrílicos , Dano ao DNA , Metilação de DNA , Diabetes Mellitus Experimental , Glucosídeos , Estresse Oxidativo , Animais , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Metilação de DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Hipoglicemiantes/farmacologia , Testes para Micronúcleos , Reparo do DNA/efeitos dos fármacos , Ensaio Cometa
18.
Sci Total Environ ; 934: 173296, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761950

RESUMO

This study explored the redox-mediated changes in a lead (Pb) contaminated soil (900 mg/kg) due to the addition of solar cell powder (SC) and investigated the impact of biochar derived from soft wood pellet (SWP) and oil seed rape straw (OSR) (5% w/w) on Pb immobilization using an automated biogeochemical microcosm system. The redox potential (Eh) of the untreated (control; SC) and biochar treated soils (SC + SWP and SC + OSR) ranged from -151 mV to +493 mV. In SC, the dissolved Pb concentrations were higher under oxic (up to 2.29 mg L-1) conditions than reducing (0.13 mg L-1) conditions. The addition of SWP and OSR to soil immobilized Pb, decreased dissolved concentration, which could be possibly due to the increase of pH, co-precipitation of Pb with FeMn (hydro)oxides and pyromorphite, and complexation with biochar surface functional groups. The ability and efficiency of OSR for Pb immobilization were higher than SWP, owing to the higher pH and density of surface functional groups of OSR than SWP. Biochar enhanced the relative abundance of Proteobacteria irrespective of Eh changes, while the relative abundance of Bacteroidota increased under oxidizing conditions. Overall, we found that both OSR and SWP immobilized Pb in solar panel waste contaminated soil under both oxidizing and reducing redox conditions which may mitigate the potential risk of Pb contamination.


Assuntos
Compostos de Cálcio , Carvão Vegetal , Chumbo , Oxirredução , Microbiologia do Solo , Poluentes do Solo , Chumbo/análise , Carvão Vegetal/química , Poluentes do Solo/análise , Compostos de Cálcio/química , Óxidos/química , Titânio/química , Solo/química , Bactérias
19.
Phys Chem Chem Phys ; 26(22): 16369-16377, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38805303

RESUMO

Graphene oxide (GO) has become the most attractive material for membrane technology owing to its potential application as a nanofiller in water treatment, purification, and desalination. In this study, we incorporated mica as a cross-linking reagent to increase the interlayer spacing and stability of GO sheets and fabricated a mica/GO (MGO) membrane for the first time. The MGO membrane (260 ± 10 nm) exhibits 100% rejection for biomolecules such as tannic acid (TA) and bovine serum albumin (BSA) and >99% rejection for multiple probe molecules, such as methylene blue, methyl orange, congo red, and rhodamine B. The high rejection of membranes can be attributed to the surface interaction of mica with GO nanosheets through covalent interaction, which enhances the stability and separation efficiency of the membranes for probe ions and molecules. This ultrathin MGO membrane also exhibits much better water permeability at 870 ± 5 L m-2 h-1 bar-1, which is 10-100 times greater than that reported for pure GO and GO-based composite membranes. Additionally, the membrane shows high rejection for salt ions (70%). Furthermore, the stability of the MGO membranes was evaluated under various conditions, and the membranes demonstrated remarkable stability for up to 60 days in a neutral environment.

20.
J Environ Manage ; 361: 121231, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38810463

RESUMO

Insitu stabilization and phytoextraction are considered as two convenient and effective technologies for the remediation of toxic elements (TEs) in soils. However, the effectiveness of these two remediation technologies together on the bioavailability and phytoextraction of TEs in field trials has not been explored yet. Specifically, the remediation potential of fly ash (FA; as stabilizing agent) and ryegrass (as a TE accumulator) intercropped with a target crop for soil polluted with multiple TEs has not been investigated yet, particularly in long-term field trials. Therefore, in this study, a six-month combined remediation field experiment of FA stabilization and/or ryegrass intercropping (IR) was carried out on the farmland soils contaminated with As, Cd, Cr, Cu, Hg, Ni, Pb and Zn where Zanthoxylumbungeanum (ZB) trees as native crops were grown for years. The treatments include soil cultivated alone with ZB untreated- (control) and treated-with FA (FA), produced by burning lignite in Shaanxi Datong power plant, China, soil cultivated with ZB and ryegrass untreated- (IR) and treated-with FA (FA + IR). This was underpinned by a large-scale survey in Daiziying (China), which showed that the topsoils were polluted by Cd, Cu, Hg and Pb, and that Hg and Pb contents in the Zanthoxylumbungeanum fruits exceeded their allowable limits. The TEs contents in the studied FA were lower than their total element contents in the soil. The DTPA-extractable TEs contents of the remediation modes were as follows: FA < FA + IR < IR < control. Notably, TEs contents in the ZB fruits were lowest under the FA + IR treatment, which were decreased by 27.6% for As, 42.3% for Cd, 16.7% for Cr, 30.5% for Cu, 23.1% for Hg, 15.5% for Ni, 33.2% for Pb and 38.1% for Zn compared with the control treatment. Whereas the FA + IR treatment enhanced TEs contents in ryegrass shoots and roots, and the TEs contents in ryegrass shoots were below their regulatory limits for fodder crops. The findings confirmed that the combined remediation strategy, i.e., FA (with low content of TEs) stabilization effect and intercropping of ZB (target crop) and ryegrass (accumulating plant) could provide a prospective approach to produce target plants within safe TEs thresholds with greater economic benefits, while remediating soils polluted with multiple TEs and mitigating the potential ecological and human health risk. Those results are of great applicable concern.


Assuntos
Cinza de Carvão , Lolium , Poluentes do Solo , Solo , Lolium/crescimento & desenvolvimento , Lolium/metabolismo , Poluentes do Solo/metabolismo , Solo/química , China , Recuperação e Remediação Ambiental/métodos , Biodegradação Ambiental , Metais Pesados
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