Exposure to chemical pollution can induce genetic and epigenetic alterations, developmental changes, and reproductive disorders, leading to population declines in polluted environments. These effects ...are triggered by chemical modifications of DNA nucleobases (DNA adducts) and epigenetic dysregulation. However, linking DNA adducts to the pollution load in situ remains challenging, and the lack of evidence-based DNA adductome response to pollution hampers the development and application of DNA adducts as biomarkers for environmental health assessment. Here, we provide the first evidence for pollution effects on the DNA modifications in wild populations of Baltic sentinel species, the amphipod Monoporeia affinis. A workflow based on high-resolution mass spectrometry to screen and characterize genomic DNA modifications was developed, and its applicability was demonstrated by profiling DNA modifications in the amphipods collected in areas with varying pollution loads. Then, the correlations between adducts and the contaminants level (polycyclic aromatic hydrocarbons (PAHs), trace metals, and pollution indices) in the sediments at the collection sites were evaluated. A total of 119 putative adducts were detected, and some (5-me-dC, N6-me-dA, 8-oxo-dG, and dI) were structurally characterized. The DNA adductome profiles, including epigenetic modifications, differed between the animals collected in areas with high and low contaminant levels. Furthermore, the correlations between the adducts and PAHs were similar across the congeners, indicating possible additive effects. Also, high-mass adducts had significantly more positive correlations with PAHs than low-mass adducts. By contrast, correlations between the DNA adducts and trace metals were stronger and more variable than for PAHs, indicating metal-specific effects. These associations between DNA adducts and environmental contaminants provide a new venue for characterizing genome-wide exposure effects in wild populations and apply DNA modifications in the effect-based assessment of chemical pollution.
Soil filamentous fungi play a prominent role in regulating ecosystem functioning in terrestrial ecosystems. This necessitates understanding their responses to climate change drivers in order to ...predict how nutrient cycling and ecosystem services will be influenced in the future. Here, we provide a quantitative synthesis of ten studies on soil fungal community responses to elevated CO
2
. Many of these studies reported contradictory diversity responses. We identify the duration of the study as an influential parameter that determines the outcome of experimentation. Our analysis reconciles the existing globally distributed experiments on fungal community responses to elevated CO
2
and provides a framework for comparing results of future CO
2
enrichment studies.
Recent studies have suggested that uremic toxins such as indoxyl sulfate (IS) and indole-3-acetic acid (IAA) from the metabolism of the gut microbiota may be involved in the inflammatory signaling ...pathway in chronic kidney disease (CKD) patients through the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The objective of this study was to investigate the possible relationship between uremic toxins (IS and IAA) and AhR protein expression in CKD patients. A cross-sectional observational study involving 17 hemodialysis (HD) 11 men, 55.5 ± 11.7 years of age, 54.0 (25.5–136.0) months of HD, body mass index (BMI) of 25.8 ± 3.8 kg/m2 and 15 non-dialysis-dependent (NDD) CKD (8 men, 54.1 ± 18.2 years of age, glomerular filtration rate of 34.8 ± 21.0 mL/min/1.73 m2, BMI of 27.4 ± 5.0 kg/m2) patients was conducted. IS and IAA levels were measured by reversed-phase high-performance liquid chromatography, and the protein expression levels of AhR and nuclear factor κ B (NF-κB) were evaluated by a Western blot assay. There was no difference in the expression of either AhR or NF-κB in the patients, and as expected, uremic toxin levels were higher in HD patients than in NDD patients. In the overall analysis, AhR protein expression was positively associated with IAA plasma levels (r = 0.4; p = 0.03) and NF-κB protein expression (r = 0.62; p = 0.001). Although the role of AhR in inflammation and CVD in CKD patients is far from being completely understood, the association between IAA and AhR observed in this study suggests a possible role for uremic toxins in the cell signaling pathway involved in inflammation in CKD patients.
Tuberculosis is a disease with high incidence and high mortality rate, especially in Brazil. Although there are several medications available for treatment, in cases of resistance, there is a need to ...use more than one medication.
Therefore, cases of toxicity increase and reports of resistance have been worrying the population. In addition, some medications have a short period of effectiveness. To achieve the goal, ligand-based and structure-based approaches were used.
Thus, in an attempt to discover potent inhibitors against Mycobacterium tuberculosis enzymes, we sought to identify natural products with high therapeutic potential for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies.
The results showed that the models generated from two sets of molecules with known activity against M. tuberculosis enzymes InhA and PS were able to select 11 and 8 compounds, respectively, between Lignans and Neolignans with 50 to 60% activity probability. In addition, molecular docking contributed to confirm the mechanism of action of compounds and increase the accuracy of methodologies. All molecules showed higher binding energy values for the drug Isoniazid. We conclude that compounds 33, 34, 110, 114 and 133 are promising for InhA target and compounds 07, 08, 19, 21, 42, 48, 75 and 141 for target PS. In addition, most molecules did not show any toxicity according to the evaluated parameters.
Therefore, Lignans and Neolignans may be an alternative for the treatment of Tuberculosis.
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•LC-ESI-MS/MS analysis identified various phenolics in Annona crassiflora fruit peel.•Liquid-liquid partitioning increased the phenolics in polar fractions (EtAc and But).•EtAc and ...But showed high antioxidant capacity and low cytotoxicity.•The repertoire of bioactive compounds inhibited glycoside hydrolases and glycation.
Annona crassiflora Mart., whose fruit is popularly known as araticum, is a member of the Annonaceae family found in the Brazilian Cerrado. Although this plant has several medicinal uses, its bioactive molecules are not fully understood. A bioguided assay was performed to identify the main bioactive compounds of A. crassiflora fruit peel from the ethanol extract fractions with antioxidant capacity and α-amylase, α-glucosidase and glycation inhibitory activities. Ethyl acetate and n-butanol fractions showed, respectively, higher antioxidant capacity (DPPH IC50 1.5±0.1 and 0.8±0.1μgmL−1, ORAC 3355±164 and 2714±79μmoltroloxeq/g, and FRAP 888±16 and 921±9μmoltroloxeq/g) and inhibitory activities against α-amylase (IC50 4.5±0.8 and 1.7±0.3μgmL−1), α-glucosidase (IC50 554.5±158.6 and 787.8±140.6μgmL−1) and glycation (IC50 14.3±3.3 and 16.0±4.2μgmL−1), and lower cytotoxicity, compared to the other fractions and crude ethanol extract. The HPLC-ESI-MS/MS analysis identified various biomolecules known as potent antioxidants, such as chlorogenic acid, (epi)catechin, procyanidins, caffeoyl-hexosides, quercetin-glucosides and kaempferol. The fruit peel of A. crassiflora, a specie from Cerrado, the Brazilian Savanna, provided a source of antioxidant compounds with properties to block carbohydrate digestive enzymes and formation of glycation products. Thus, there is potential to use the by-products of araticum in order to identify and isolate phytochemicals for application in nutraceutical supplements, food additives and pharmaceuticals products.
Purpose
Regular physical exercise may result in many benefits to patients with chronic kidney disease (CKD) on hemodialysis (HD), including gut microbiota modulation and solute removal. The study ...aimed to evaluate the effects of two programs of intradialytic exercises on uremic toxins plasma levels in HD patients.
Methods
In experiment 1, twenty HD patients 12 men, 44.1 ± 8.9 years, BMI of 23.4 ± 2.4 kg/m
2
were randomized into two groups: Aerobic exercise group (AEG,
n
= 11) that performed aerobic exercise on an adapted exercise bike three times a week for three months (36 sessions) and Control group (CG,
n
= 9). In experiment 2, twenty-six HD patients 19 men, 47.6 ± 11.0 years, BMI of 25.9 ± 3.6 kg/m
2
were randomized into Resistance exercise group (REG,
n
= 14) that performed a resistance exercise program (using elastic bands and ankle cuffs with both lower limbs) monitored three times a week, during six months (72 sessions) and CG (
n
= 12). P-cresyl sulfate (p-CS), indoxyl sulfate (IS), and indol-3-acetic acid (IAA) plasma levels were determined by high-performance liquid chromatography (HPLC) with fluorescent detection.
Results
The uremic toxins plasma levels did not reduce in both exercise programs, aerobic exercise (IS: 32.7 ± 14.0 vs 33.0 ± 15.4 mg/L,
p
= 0.86; p-CS: 59.9 ± 39.3 vs 60.0 ± 41.2 mg/L,
p
= 0.99; IAA: 2233 1488–2848 vs 2227 1275–2824 µg/L, p = 0.72) and resistance exercise (IS: 28.3 ± 11.3 vs 29.1 ± 9.7 mg/L,
p
= 0.77; p-CS: 31.4 ± 21.3 vs 34.2 ± 19.8 mg/L,
p
= 0.63; IAA: 1628 1330–3530 vs 2000 971–3085 µg/L,
p
= 0.35) in HD patients.
Conclusion
According to our findings, physical exercise does not appear to alter the levels of uremic toxins produced by the gut microbiota in HD patients.
Purpose
In chronic kidney disease (CKD) patients, dysbiosis is associated with inflammation and cardiovascular risk, so many nutritional strategies are being studied to reduce these complications. ...Resistant starch (RS) can be considered a prebiotic that promotes many benefits, including modulation of gut microbiota which is linked to immune-modulatory effects. The aim of this study was to evaluate the effects of RS supplementation on proinflammatory cytokines in CKD patients on hemodialysis (HD).
Methods
A double-blind, placebo-controlled, randomized trial was conducted with sixteen HD patients (55.3 ± 10.05 years, body mass index (BMI) 25.9 ± 5.42 kg/m
2
, 56% men, time on dialysis 38.9 ± 29.23 months). They were allocated to the RS group (16 g RS/day) or placebo group (manioc flour). The serum concentration of ten cytokines and growth factors was detected through a multiparametric immunoassay based on XMap-labeled magnetic microbeads (Luminex Corp, USA) before and after 4 weeks with RS supplementation.
Results
After RS supplementation, there was a reduction of Regulated upon Activation, Normal T-Cell Expressed and Secreted (
p <
0.001), platelet-derived growth factor (two B subunits) (
p
= 0.014) and interferon-inducible protein 10 (IP-10) (
p
= 0.027). The other parameters did not change significantly.
Conclusion
This preliminary result indicates that RS may contribute to a desirable profile of inflammatory markers in CKD patients.
We investigated changes in the phenolic profile and antioxidant properties in the extracts of developing seeds of açaí (
). Four developmental stages were evaluated, with earlier stages displaying ...higher antioxidant activity and polyphenols content, while mass spectrometry analysis identified procyanidins (PCs) as the major components of the extracts in all stages. B-type PCs varied from dimers to decamers, with A-type linkages in a smaller number. Extracted PCs decreased in average length from 20.5 to 10.1 along seed development. PC composition indicated that (-)-epicatechin corresponded to over 95% of extension units in all stages, while (+)-catechin presence as the starter unit increased from 42 to 78.8% during seed development. This variation was correlated to the abundance of key enzymes for PC biosynthesis during seed development. This study is the first to report PC content and composition variations during açaí seed development, which can contribute to studies on the plant's physiology and biotechnological applications.
Tetrahydrolinalool (THL) is an acyclic monoterpene alcohol, produced during linalol metabolism and also a constituent of essential oils. As described in the literature, many monoterpenes present ...anticonvulsant properties, and thus we became interested in evaluating the anticonvulsant activity of Tetrahydrolinalool using in mice model as well as in silico approaches. Our results demonstrated that THL increased latency to seizure onset and also reduced the mortality, in picrotoxin induced seizure tests. The results may be related to GABAergic regulation, which was also suggested in seizure testing induced by 3‐mercapto‐propionic acid. In the strychnine‐induced seizure testing, none of the groups pretreated with THL modulated the parameters indicative of anticonvulsant effect. The electrophysiological results revealed that THL treatment reduces seizures induced by pentylenetetrazole. The in silico molecular docking studies showed that the interaction between THL and a GABAA receptor model formed a stable complex, in comparison to the crystaligraphic structure of diazepam, a structurally related ligand. In conclusion, all the evidences showed that THL presents effective anticonvulsant activity related to the GABAergic pathway, being a candidate for treatment of epileptic syndromes
Ethics Approval Statement: The protocols in this research were previously approved by the Ethics Committee on the Use of Animals (CEUA #082/2017) of the Federal University of Paraíba, Brazil.
•ZnCo coatings were successfully electrodeposited on Cu substrate from deep eutectic solvent.•ZnCo electrocatalysts were electrodeposited potentiostatically by a simple methodology without ...additives.•ZnCo electrocatalysts showed good electroactivity and stability for hydrogen evolution reaction.
Hydrogen has emerged as a clean and renewable energy and its production by water splitting is a promising production route. However, to meet the demand on a commercial scale, research focusing on more efficient electrocatalysts is necessary. In this work, new findings on Zn, Co and Zn-Co coatings produced in deep eutectic solvent based on choline chloride (ChCl) and ethylene glycol (EG) are reported. Varying the concentrations of Zn2+ and Co2+ ions in 1ChCl:2EG, crystalline electrodeposits with fine control of composition and morphology were obtained, and which present different reactivity to electrocatalyze the hydrogen evolution reaction (HER) in alkaline medium. The performance of metallic coatings is influenced by temperature, due to changes in viscosity, ionic diffusion coefficient and charge transport in the electrolyte. The results also revealed that increasing the Co content in the coatings, changes occur in the morphological organization, stability, and electrode area, which positively influence the hydrogen production. Among the different coatings tested (Zn, Co, Zn96-Co4 and Zn3-Co97), Zn3-Co97 was the most promising in terms of Tafel coefficient (108 mV dec–1), exchange current density (8.57 × 10−6 A cm−2) and overpotential estimated for HER (333 mV at 10 mA cm−2) in 1 mol L–1 KOH at 298.15 K, although the other materials also showed electrochemical advantages over the unmodified Cu substrate. The reported data also reiterate the great electrochemical potential of metallic coatings for water splitting and complement the growing energy demand for hydrogen gas.
