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Work-related Exposures to be able to Natural Chemicals and also Asthma Signs and symptoms in the CONSTANCES Cohort.
Finally, a docking study was also performed using MTB DNA Gyrase (PDB ID 5BS8) for the significantly active compound 8a to know the exact binding pattern within the active site of the target enzyme.Indole-benzimidazoles have recently gained attention due to their antiproliferative and antiestrogenic effects. However, their structural similarities and molecular mechanisms shared with selective estrogen receptor modulators (SERMs) have not yet been investigated. In this study, we synthesized novel ethylsulfonyl indole-benzimidazole derivatives by substituting the first (R1) and fifth (R2) positions of benzimidazole and indole groups, respectively. Subsequently, we performed 1H NMR, 13C NMR, and Mass spectral and in silico docking analyses, and anticancer activity screening studies of these novel indole-benzimidazoles. The antiproliferative effects of indole-benzimidazoles were found to be more similar between the estrogen (E2) responsive cell lines MCF-7 and HEPG2 in comparison to the Estrogen Receptor negative (ER-) cell line MDA-MB-231. R1p-fluorobenzyl group members were selected as lead compounds for their potent anticancer effects and moderate structural affinity to ER. Microarray expression profiling and gene enrichment analyses (GSEA) of the selected compounds (R1p-fluorobenzyl 48, 49, 50, 51; R13,4-difluorobenzyl 53) helped determine the similarly modulated cellular signaling pathways among derivatives. Moreover, we identified known compounds that have significantly similar gene signatures to that of 51 via queries performed in LINCS database; and further transcriptomics comparisons were made using public GEO datasets (GSE35428, GSE7765, GSE62673). Our results strongly demonstrate that these novel indole-benzimidazoles can modulate ER target gene expression as well as dioxin-mediated aryl hydrocarbon receptor and amino acid deprivation-mediated integrated stress response signaling in a dose-dependent manner.Enterococci are gram-positive, widespread nosocomial pathogens that in recent years have developed resistance to various commonly employed antibiotics. Since finding new infection-control agents based on secondary metabolites from organisms has proved successful for decades, natural products are potentially useful sources of compounds with activity against enterococci. Herein are reported the results of a natural product library screening based on a whole-cell assay against a gram-positive model organism, which led to the isolation of a series of anacardic acids identified by analysis of their spectroscopic data and by chemical derivatizations. Merulinic acid C was identified as the most active anacardic acid derivative obtained against antibiotic-resistant enterococci. Fluorescence microscopy analyses showed that merulinic acid C targets the bacterial membrane without affecting the peptidoglycan and causes rapid cellular ATP leakage from cells. Merulinic acid C was shown to be synergistic with gentamicin against Enterococcus faecium, indicating that this compound could inspire the development of new antibiotic combinations effective against drug-resistant pathogens.Polycyclic aromatic hydrocarbons (PAHs) are compounds known for their adverse effects on human health. Many of them are proven carcinogens, especially those with 5 and 6 aromatic rings, which under normal tropospheric conditions are found in the particle-phase. Benzo(a)pyrene (BaP) is often measured as their general representative. Sarajevo, the capital of Bosnia and Herzegovina, is among the European cities with the poorest air quality. However, in Sarajevo PAHs are neither routinely measured within the air quality monitoring network nor have been a subject of extended, continuous field studies during the most polluted cold periods of the year. The capital of Croatia, Zagreb, is located approximately 300 km air distance north-west from Sarajevo. PAH mass concentrations in Zagreb have been measured continuously since 1994 within air quality monitoring networks. During winter 2017/2018, the SAFICA project (Sarajevo Canton Winter Field Campaign 2018) was carried out in order to characterize the chemical composiion of other liquid fossil fuels (petroleum and fuel oil). Wood burning was occasionally indicated as a PAH emission source in Zagreb, while in Sarajevo the contribution of PAHs from wood and coal combustion was more evident. Calculated value for total carcinogenic potency (TCP) of PAHs, which was estimated using toxic equivalence factors from the literature, in PM10 samples collected in Sarajevo was more than twice higher than in Zagreb (10.6 ng m-3 and 4.7 ng m-3, respectively). BaP had the highest contribution to the TCP at both locations (69 and 67%).The high aggregation ability of anammox granular sludge is an issue of wide concern; however, the mechanism needs to be further clarified. In this study, selective hydrolysis experiments were performed to determine the role of exopolysaccharide (PS) branched chains and proteins for the aggregation mechanism of anammox granular sludge. The results revealed that selective hydrolysis of proteins hardly affected the granular aggregation while the hydrolysis of PS branched chains led to a decrease in the sludge zeta potential by 17.3% (β-amylase group) and 24.1% (isoamylase group), a decrease of hydrophobicity by 11.6% (β-amylase group) and 17.7% (isoamylase group), an increase of surface free energy by 36.8% (β-amylase group) and 55.1% (isoamylase group) and the deterioration of the PS self-assembly ability. In addition, FTIR and XPS spectra analysis showed that the disruption of PS branched chains resulted in a higher proportion of hydrophilic and electronegative groups, which hindered bacterial aggregation, which was further confirmed by XDLVO theory. The key role of the PS chain structure in sludge aggregation is a critical finding of this work that provides helpful insights for the application of anammox process.Soil samples adjacent to ten CCA-treated utility poles were collected, sieved into four fractions ( Cu using GS solution. For all elements, inhalation bioaccessibility (% and mg/kg) using ALF was higher than oral bioaccessibility, except for Pb bioaccessibility (mg/kg) in two samples. However, solubility of metal(loid)s in GS presented the lowest values. Copper showed the highest oral and inhalation bioaccessibility (%) and Cr showed the lowest. find more Moreover, organic matter content and cation exchange capacity in particle size 90-20 μm were negatively correlated with Cu and Pb oral bioaccessibility (%).
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