The effects of triclosan (TCS) and its transformation product methyl-triclosan (MTCS) on the earthworm Eisenia fetida were investigated using Gas chromatography-mass spectrometry (GC-MS) metabolomics. Earthworms were exposed to 0, 0.25, 1, 4, 16, and 64 µg g^-1 of either TCS or MTCS for 14 days in commercial worm bedding. Only MTCS exposure caused any effects on the earthworm metabolites targeted in this study. Succinic acid was elevated relative to the control at concentrations ≥ 0.25 µg g^-1 and glucose was elevated at 1 µg g^-1. Earthworms exposed to 1 µg g^-1 MTCS had the greatest separation from the control using Principal Components Analysis (PCA), while 0.25 and 1 µg g^-1 had the largest separation in Discriminant Analysis (DA). Essential amino acids valine, leucine, serine, and phenylalanine had large, standardized coefficients for PCA and DA reflecting their contribution to separation, suggesting that essential amino acid homeostasis was perturbed by MTCS. Malic acid, succinic acid, margaric acid, and glucose were highly correlated (p < 0.01) with Canonical 1 and PC 2, while maltose was correlated with Canonical 2 and PC 7, indicating a strong relationship between these metabolites and the multivariate separation expressed in the canonical variables. Disruption of succinate metabolism by membrane destabilization in mitochondria was hypothesized as a possible mode of action for MTCS.

01 Jan 2024·International Journal of Biological Macromolecules

Removal of aflatoxin B1 from contaminated milk and water by nitrogen/carbon-enriched cobalt ferrite -chitosan nanosphere: RSM optimization, kinetic, and thermodynamic perspectives

Article

Author: Faraji, A R ; Moradian, M ; Davood, A

In view of the feed/foods inevitably contaminated by toxic and carcinogenic aflatoxin B1 (AFB₁), efficient mesoporous metformin-chitosan/silica‑cobalt ferrite nanospheres (Mt-CS/CFS NSs) was prepared to remove AFB₁ from aqueous/non-aqueous media. The morphological, functional, and structural characteristics and adsorption properties of C/N-enriched CS/CFS were investigated systematically. The interactive operating variables (temperature (5.0-35 °C); time (10-100 min); AFB₁ dose (50-100 μg/mL); and Mt-CS/CFS dosage (0.5-3.5 mg) were optimized via the Box-Behnken design (BBD), which demonstrated good agreement between the experimental data and proposed model. The adsorption efficiency in artificially contaminated cow's milk as well as aqueous environment reached over 91.0 % in a wide pH range (3.0-9.0), without significant change in the nutritional value of milk. Freundlich isotherm and second-order adsorption kinetics were regarded as the most suitable models to fit the adsorption results, and the adsorption rate is dominated by the intra-particle diffusion and boundary layer diffusion. Thermodynamic analyses proved that the process was spontaneous and exothermic. The adsorption mechanism could be explained as physisorption via hydrogen bonding, n-π interaction, and hydrophobic/hydrophilic interactions. The porous Mt-CS/CFS NS derived from chitosan nanoparticles is therefore outstanding adsorbent, offering great adsorptive performance and recycabilities, which impedes economic losses in the food industry.

31 Dec 2023·Journal of Enzyme Inhibition and Medicinal Chemistry

Inhibition of pathogenic bacterial carbonic anhydrases by monothiocarbamates

Article

Author: Giovannuzzi, Simone ; Nocentini, Alessio ; Marapaka, Anil Kumar ; Seleem, Mohamed N. ; Flaherty, Daniel P. ; Abutaleb, Nader S. ; Pisano, Luigi ; Supuran, Claudiu T. ; Liang, Hsin-Wen ; Carta, Fabrizio

Carbonic anhydrases (CAs) from the pathogenic bacteria Nesseria gonorrhoeae and vancomycin-resistant enterococci (VRE) have recently been validated as antibacterial drug targets. Here we explored the inhibition of the α-CA from N. gonorrhoeae (α-NgCA), of α- and γ-class enzymes from Enterococcus faecium (α-EfCA and γ-EfCA) with a panel of aliphatic, heterocyclic and aryl-alkyl primary/secondary monothiocarbamates (MTCs). α-NgCA was inhibited in vitro with K_Is ranging from 0.367 to 0.919 µM. The compounds inhibited the α-EfCA and γ-EfCA with K_I ranges of 0.195-0.959 µM and of 0.149-1.90 µM, respectively. Some MTCs were also investigated for their inhibitory effects on the growth of clinically-relevant N. gonorrhoeae and VRE strains. No inhibitory effects on the growth of VRE were noted for all MTCs, whereas one compound (13) inhibited the growth N. gonorrhoeae strains at concentrations ranging from 16 to 64 µg/mL. This suggests that compound 13 may be a potential antibacterial agent against N. gonorrhoeae.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 1	China	Beijing Xiangtianmu Biology Science & Technology Co., Ltd.	-

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