(E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs.

Non-enzymatic thiol addition into the α,ß-unsaturated carbonyl system is associated with several biological effects. In vivo, the reactions can form small-molecule thiol (e.g., glutathione) or protein thiol adducts. The reaction of two synthetic (4'-methyl- and 4'-methoxy substituted) cyclic chalcone analogs with reduced glutathione (GSH) and N-acetylcysteine (NAC) was studied by (high-pressure liquid chromatography-ultraviolet spectroscopy) HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The structure of the formed adducts was confirmed by (high-pressure liquid chromatography-mass spectrometry) HPLC-MS. The incubations were performed under three different pH conditions (pH 3.2/3.7, 6.3/6.8, and 8.0/7.4). The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended on the substitution and the pH. The frontier molecular orbitals and the Fukui function were carried out to investigate the effects on open-chain and seven-membered cyclic analogs. Furthermore, machine learning protocols were used to provide more insights into physicochemical properties and to support the different thiol-reactivity. HPLC analysis indicated diastereoselectivity of the reactions. The observed reactivities do not directly relate to the different in vitro cancer cell cytotoxicity of the compounds.

Comparative Study on Grape Berry Anthocyanins of Various Teinturier Varieties.

The red-fleshed grape cultivars, called teinturier or dyer grapes, contain anthocyanins in both the skin and flesh. These phenolic compounds exhibit excellent coloring ability, and as antioxidants, they are important bioactive compounds in food crops. In this work, anthocyanin patterns of grape berries of fifteen teinturier varieties collected from the gene bank located at Pécs in the southwest of Hungary were compared. Anthocyanin profiles of numerous varieties originating from Hungary such as 'Bíborkadarka', 'Kármin', 'Kurucvér', and 'Turán' are reported for the first time. Anthocyanins extracted separately from the skin and juice were analyzed using high-performance liquid chromatography coupled with a photodiode array detector. For the identification of compounds, high-resolution orbitrap mass spectrometry was used. All in all, twenty-one anthocyanins were identified and quantified. We found that anthocyanin patterns differed significantly in the skin and juice for all investigated cultivars. For Vitis vinifera varieties, the predominant anthocyanin in the skin was malvidin-3-O-glucoside, while the main pigment in the juice was peonidin-3-O-glucoside. For the first time, a significant amount of diglucosides was detected in two Vitis Vinifera cultivars with a direct relationship. In general, the pigment composition of the skin was much more complex than that of the juice. The comparative study with presented patterns gives valuable and beneficial information from a chemotaxonomical point of view. Our results also help to choose the appropriate teinturier varieties with the desired anthocyanins for food coloring or winemaking purposes.

The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia.

Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyzed oxidative metabolites. The present work aimed to investigate how experimental hyperglycemia affects the intestinal and biliary appearance of the oxidative and Phase II metabolites of ibuprofen in rats. In vivo studies were performed by luminal perfusion of 250 µM racemic ibuprofen solution in control and streptozotocin-treated (hyperglycemic) rats. Analysis of the collected intestinal perfusate and bile samples was performed by HPLC-UV and HPLC-MS. No oxidative metabolites could be detected in the perfusate samples. The biliary appearance of ibuprofen, 2-hydroxyibuprofen, ibuprofen glucuronide, hydroxylated ibuprofen glucuronide, and ibuprofen taurate was depressed in the hyperglycemic animals. However, no specific non-enzymatic (hydroxyl radical initiated) hydroxylation product could be detected. Instead, the depression of biliary excretion of ibuprofen and ibuprofen metabolites turned out to be the indicative marker of hyperglycemia. The observed changes impact the pharmacokinetics of drugs administered in hyperglycemic individuals.

Antibacterial Effect of Lemongrass (Cymbopogoncitratus) against the Aetiological Agents of Pitted Keratolyis.

Pitted keratolysis (PK) is a bacterial skin infection mostly affecting the pressure-bearing areas of the soles, causing unpleasant symptoms. Antibiotics are used for therapy, but the emergence of antiobiotic resistance, makes the application of novel topical therapeutic agents necessary. The antibacterial effects of 12 EOs were compared in the first part of this study against the three known aetiological agents of PK (Kytococcus sedentarius, Dermatophilus congolensis and Bacillus thuringiensis). The results of the minimal inhibitory concentration, minimal bactericidal concentration and spore-formation inhibition tests revealed that lemongrass was the most effective EO against all three bacterium species and was therefore chosen for further analysis. Seventeen compounds were identified with solid-phase microextraction followed by gas chromatography-mass spectrometry (HS-SPME/GC-MS) analysis while thin-layer chromatography combined with direct bioautography (TLC-BD) was used to detect the presence of antibacterially active compounds. Citral showed a characteristic spot at the Rf value of 0.47, while the HS-SPME/GC-MS analysis of an unknown spot with strong antibacterial activity revealed the presence of α-terpineol, γ-cadinene and calamenene. Of these, α-terpineol was confirmed to possess an antimicrobial effect on all three bacterium species associated with PK. Our study supports the hypothesis that, based on their spectrum, EO-based formulations have potent antibacterial effects against PK and warrant further investigation as topical therapeutics.

Feature Pyramid Network Based Efficient Normal Estimation and Filtering for Time-of-Flight Depth Cameras.

In this paper, an efficient normal estimation and filtering method for depth images acquired by Time-of-Flight (ToF) cameras is proposed. The method is based on a common feature pyramid networks (FPN) architecture. The normal estimation method is called ToFNest, and the filtering method ToFClean. Both of these low-level 3D point cloud processing methods start from the 2D depth images, projecting the measured data into the 3D space and computing a task-specific loss function. Despite the simplicity, the methods prove to be efficient in terms of robustness and runtime. In order to validate the methods, extensive evaluations on public and custom datasets were performed. Compared with the state-of-the-art methods, the ToFNest and ToFClean algorithms are faster by an order of magnitude without losing precision on public datasets.

Reaction of Chalcones with Cellular Thiols. The Effect of the 4-Substitution of Chalcones and Protonation State of the Thiols on the Addition Process. Diastereoselective Thiol Addition.

Several biological effects of chalcones have been reported to be associated with their thiol reactivity. In vivo, the reactions can result in the formation of small-molecule or protein thiol adducts. Both types of reactions can play a role in the biological effects of this class of compounds. Progress of the reaction of 4-methyl- and 4-methoxychalcone with glutathione and N-acetylcysteine was studied by the HPLC-UV-VIS method. The reactions were conducted under three different pH conditions. HPLC-MS measurements confirmed the structure of the formed adducts. The chalcones reacted with both thiols under all incubation conditions. The initial rate and composition of the equilibrium mixtures depended on the ratio of the deprotonated form of the thiols. In the reaction of 4-methoxychalcone with N-acetylcysteine under strongly basic conditions, transformation of the kinetic adduct into the thermodynamically more stable one was observed. Addition of S-protonated N-acetylcysteine onto the polar double bonds of the chalcones showed different degrees of diastereoselectivity. Both chalcones showed a Michael-type addition reaction with the ionized and non-ionized forms of the investigated thiols. The initial reactivity of the chalcones and the equilibrium composition of the incubates showed a positive correlation with the degree of ionization of the thiols. Conversions showed systematic differences under each set of conditions. The observed differences can hint at the difference in reported biological actions of 4-methyl- and 4-methoxy-substituted chalcones.

Reagent-induced asymmetric induction in addition reaction of reduced glutathione onto bis-Mannich chalcones.

The stereochemistry of non-enzyme catalyzed nucleophilic addition of GSH to 4'-hydroxychalcone 1 and its bis-Mannich derivative 2 was investigated at different pH values (pH 3.2, 6.1, 7.4, and 8.0). The stereochemical outcome of the reactions was evaluated by HPLC-UV-Vis method. Under strongly acidic conditions (pH 3.2), an unexpected diastereoselective addition of GSH onto the bis-Mannich derivative 2 was observed. Such a selectivity could not be observed in the similar reaction of 2 with N-acetylcysteine. The observed stereoselectivity can be rationalized by ion-pair formation between the protonated Mannich nitrogens and the deprotonated GSH(glutamate)-carboxylate. To the best of our knowledge, this is the first example of reagent-induced asymmetric induction in Michael-type additions of thiols.

Changes of fatty acid composition of human milk during the first month of lactation: a day-to-day approach in the first week.

BACKGROUND: Fatty acid composition of human milk (HM) is known to change considerably during lactation. However, we were unable to find data on changes of fatty acid composition of HM during the very early phase of lactation, i.e. in the first week of life. SUBJECTS AND METHODS: HM samples were obtained from 18 healthy lactating women every day during the first week and thereafter on the 14th and 28th days of lactation. Fatty acid composition of colostrum and mature HM samples was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Values of the n-6 essential fatty acid, linoleic acid, in HM did not change significantly during the first month of lactation, whereas values of the n-3 essential fatty acid, alpha-linolenic acid, showed significant increases during the first 2 weeks of lactation (1st day: 0.49 [0.12], % weight/weight, median [ranges from the 1st to the 3rd quartile], 14th day: 0.69 [0.31], p < 0.05). In contrast, values of the n-6 long-chain metabolites, eicosadienoic-, dihomo-gamma-linolenic- and arachidonic acid, as well as the values of the n-3 long-chain metabolites, eicosatrienoic-, and eicosapentaenoic acid exhibited significant decreases during the entire period investigated. The principal n-3 long-chain metabolite, docosahexaenoic acid, showed a significant increase between the 3rd and 14th days, but a significant decrease between the 14th and 28th days (3rd day: 0.15 [0.13], 14th day: 0.28 [0.11], p < 0.05, 28th day: 0.19 [0.12], p < 0.01). There were statistically significant positive correlations between arachidonic and docosahexaenoic acid values on the 1st (r = 0.67, p < 0.01), 5th (r = 0.56, p < 0.05) and the 6th (r = 0.53, p < 0.05) days of lactation. CONCLUSION: Fatty acid composition of HM changes significantly even during the first week of lactation. The lack of positive correlation between essential fatty acids and their long-chain metabolites suggests that it is not only the availability of essential fatty acids that influences the fatty acid composition of human colostrum.

[Fatty acid composition of colostrum and mature human milk in Hungary]. / A colostrum és az érett nói tej zsírsavösszetétele Magyarországon.

INTRODUCTION AND AIMS: Because of the lack of up-to-date data on fatty acid composition of human milk in Hungary, the authors analysed fatty acid composition of colostrum (n = 18, one hind milk sample on day 5 after delivery) and mature milk (n = 15, pooled 24 h collections repeated twice with 2 weeks intervals at median duration of lactation of 4 months) samples with high-resolution capillary gas chromatography. RESULTS: Fat content and fatty acid compositions did not differ in 24 h pooled mature human milk samples obtained with 2 weeks intervals. Significantly lower values of linoleic acid [10.98 (4.81) vs. 14.70 (5.32), % w/w, median (range from the 1st to the 3rd quartile), colostrum vs. mature human milk, p < 0.001] and alpha-linolenic acid [0.22 (0.09) vs. 0.68 (0.21), p < 0.0001], and significantly higher values of arachidonic acid [0.70 (0.56) vs. 0.50 (0.12), p < 0.001] and docosahexaenoic acid [0.22 (0.15) vs. 0.18 (0.06), p < 0.05] were found in colostrum than in mature human milk. Significant and positive correlations were seen between linoleic and arachidonic (r = 0.71, p = 0.001) as well as between alpha-linolenic and docosahexaenoic (r = 0.59, p = 0.01) acid values in colostrum, but not in mature human milk. CONCLUSION: While mature human milk linoleic, arachidonic and alpha-linolenic acid values in this study were in the range usually reported in the literature, the contribution of docosahexaenoic acid to the fatty acid composition of human milk was considerably lower in Hungary than in several other populations.

Trans isomeric octadecenoic acids are related inversely to arachidonic acid and DHA and positively related to mead acid in umbilical vessel wall lipids.

Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1-15 yr as well as in venous cord blood lipids of full-term infants. Here we report FA compositional data of cord blood vessel wall lipids in 308 healthy, full-term infants (gestational age: 39.7 +/- 1.2 wk, birth weight: 3528 +/- 429 g, mean +/- SD). The median (interquartile range) of the sum of 18-carbon trans FA was 0.22 (0.13) % w/w in umbilical artery and 0.16 (0.10) % w/w in umbilical vein lipids. Nonparametric correlation analysis showed significant inverse correlations between the sum of 18-carbon trans FA and both arachidonic acid and DHA in artery (r = -0.38, P < 0.01, and r = -0.20, P < 0.01) and vein (r = -0.36, P < 0.01, and -0.17, P < 0.01) wall lipids. In addition, the sum of 18-carbon trans FA was significantly positively correlated to Mead acid, a general indicator of EFA deficiency, in both artery (r = +0.35, P < 0.01) and vein (r = +0.31, P< 0.01) wall lipids. The present results obtained in a large group of full-term infants suggest that maternal trans FA intake is inversely associated with long-chain PUFA status of the infant at birth.