Lignans in flowering aerial parts of Linum species – Chemodiversity in the light of systematics and phylogeny

The aerial parts of 54 accessions representing 41 Linum species and four species of related genera were analysed for lignans by means of HPLC-ESI/MS–MS-UV/DAD. In total, 64 different lignans of the aryltetralin-, arylnaphthalene-, aryldihydronaphthalene-, dibenzylbutyrolactone-, and furofuran type were identified. According to their lignan profile, the Linum species can be divided in two groups accumulating as major lignan types either cyclolignans of the aryltetralin-series on one hand, or aryldihydronaphthalenes/arylnaphthalenes, on the other. Five of the investigated Linum species did not contain any detectable amounts of these lignans under the chosen analytical conditions. Furthermore, none of the lignans identified in Linum species was detectable in representatives of three related genera, namely, Reinwardtia (Linaceae, Linoideae), Hugonia and Indorouchera (Linaceae, Hugonioideae).The two species groups differing in the types of the dominating cyclolignans comprise representatives of the major taxonomic sections. Representatives of sections Syllinum, Cathartolinum and Linopsis accumulate mainly aryltetralins while those of sections Linum and Dasylinum were found to contain mainly aryldihydronaphthalenes/-naphthalenes. These phytochemical data correlate very well with a recent study on the molecular phylogeny of Linum/Linaceae, where a subdivision of Linum into two major clades comprising representatives of the two mentioned groups was found. Thus, the distribution of lignans apparently reflecting phylogenetic interrelations at the infrageneric level, a plausible scenario for the evolution of lignan biosynthesis in the genus Linum can now be presented.     

Selenium Inhibits Proliferation Signaling and Restores Sodium/Potassium Pump Function of Diabetic Rat Aorta

Diabetes is characterized with increased oxidant stress, vasculopathy, and neuropathy. In diabetic vasculopathy, the observed thickening of the media and intima is not only a result of vascular smooth muscle cell proliferation but also due to modification of the extracellular matrix by these cells. Also, there is hampered membrane function and a reduction in sodium pump expression in the vessels of the diabetic animals. Selenium, being a trace element, has both insulinomimetic and antioxidant effects. Thus, we hypothesized that selenium treatment will reduce proliferation, restore physiology, and correct increased proliferation signaling of diabetic aorta. Diabetes was induced by streptozotocin (50 mg/kg body weight), and rats were then treated with sodium selenate (15 mumol/kg body weight/day) for 4 weeks. Our data from diabetic rats showed an increase in proliferation rate and matrix metalloproteinase activity in aortic cell cultures. We observed marked increases in MAPK phosphorylation and caveolin 1 expression but a decrease in Na(+)/K(+) ATPase activity in diabetic rat aorta homogenates. Selenium treatment resulted in complete normalization of the above parameters to control level, while it increased Na(+)/K(+) pump activity by 40%. Our results suggest that selenium treatment of diabetics can play beneficial role in protecting vascular architecture and function against diabetes-induced pathology.     

Protective effect of selenium treatment on diabetes-induced myocardial structural alterations

One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 μmol/kg body wt/d sodium selenite (Na₂SeO₃) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment. Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is used under control conditions.     

Sex-related effects on diabetes-induced alterations in calcium release in the rat heart

The present study was designed to determine whether the properties of local Ca(2+) release and its related regulatory mechanisms might provide insight into the role of sex differences in heart functions of control and streptozotocin-induced diabetic adult rats. Left ventricular developed pressure, the rates of pressure development and decay (+/-dP/dt), basal intracellular Ca(2+) level ([Ca(2+)](i)), and spatiotemporal parameters of [Ca(2+)](i) transients were found to be similar in male and female control rats. However, spatiotemporal parameters of Ca(2+) sparks in cardiomyocytes isolated from control females were significantly larger and slower than those in control males. Diabetes reduced left ventricular developed pressure to a lower extent in females than in males, and the diabetes-induced depressions in both +dP/dt and -dP/dt were less in females than in males. Diabetes elicited a smaller reduction in the amplitude of [Ca(2+)](i) transients in females than in males, a smaller reduction in sarcoplasmic reticulum-Ca(2+) load, and less increase in basal [Ca(2+)](i). Similarly, the elementary Ca(2+) events and their control proteins were clearly different in both sexes, and these differences were more marked in diabetes. Diabetes-induced depression of the Ca(2+) spark amplitude was significantly less in females than in matched males. Levels of cardiac ryanodine receptors (RyR2) and FK506-binding protein 12.6 in control females were significantly higher than those shown in control males. Diabetes induced less RyR2 phosphorylation and FK506-binding protein 12.6 unbinding in females. Moreover, total and free sulfhydryl groups were significantly less reduced, and PKC levels were less increased, in diabetic females than in diabetic males. The present data related to local Ca(2+) release and its related proteins describe some of the mechanisms that may underlie sex-related differences accounting for females to have less frequent development of cardiac diseases.     

Design,synthesis and docking study of novel coumarin ligands as potential selective acetylcholinesterase inhibitors

New coumaryl-thiazole derivatives with the acetamide moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and in vitro tested as acetylcholinesterase (AChE) inhibitors. 2-(diethylamino)-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)acetamide (6c, IC₅₀ value of 43?nM) was the best AChE inhibitor with a selectivity index of 4151.16 over BuChE. Kinetic study of AChE inhibition revealed that 6c was a mixed-type inhibitor. Moreover, the result of H4IIE hepatoma cell toxicity assay for 6c showed negligible cell death. Molecular docking studies were also carried out to clarify the inhibition mode of the more active compounds. Best pose of compound 6c is positioned into the active site with the coumarin ring wedged between the residues of the CAS and catalytic triad of AChE. In addition, the coumarin ring is anchored into the gorge of the enzyme by H-bond with Tyr130.     

Synthesis,biological activity and multiscale molecular modeling studies for coumaryl-carboxamide derivatives as selective carbonic anhydrase IX inhibitors

New coumaryl-carboxamide derivatives with the thiourea moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms hCA I, II, VII and IX were evaluated. While the hCA I, II and VII isoforms were not inhibited by the investigated compounds, the tumour-associated isoform hCA IX was inhibited in the high nanomolar range. 2-Oxo-N-((2-(pyrrolidin-1-yl)ethyl)carbamothioyl)-2H-chromene-3-carboxamide (e11) exhibited a selective inhibitory action against hCA IX with the K_i of 107.9?nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modeling approaches were used. Different molecular docking algorithms were used to investigate binding poses and predicted binding energies of studied compounds at the active sites of the CA I, II, VII and IX isoforms.     

Selenium treatment protects diabetes-induced biochemical and ultrastructural alterations in liver tissue

We have shown that a single dose of streptozotocin (STZ) (50 mg/kg body weight) injected into rats caused significant changes in some antioxidant enzyme activities, such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities, and acid-soluble sulfhydryl levels of the liver tissue with respect to the control rats. Furthermore, these alterations in the activities of the antioxidant enzymes were accompanied by significant changes in the ultrastructure of the liver tissue; mainly intercellular biliary canaliculi were distended and contained stagnant bile, swollen mitochondria in hepatocytes and disoriented and disintegrating cristae, dilatation of the rough endoplasmic reticulum (rER) with detachment of ribosomes, and dissociation of polysomes. Both diabetic and normal rats were treated with sodium selenite (5 micromol/kg/d, intra peritoneally) for 4 wk following 1 wk of diabetes induction. This treatment of diabetic rats improved significantly diabetes-induced alterations in liver antioxidant enzymes. Moreover, treating of diabetic rats with sodium selenite prevented primarily the variation in staining quality of hepatocytes nuclei, increased density and eosinophilia of the cytoplasm, focal sinusoidal dilatation and congestion, and increased numbers of mitochondria with different size and shape. In summary, treatment of diabetic rats with sodium selenite has beneficial effects on both antioxidant system and the ultrastructure of the liver tissue. These findings suggest that diabetes-induced oxidative stress can be responsible for the development of diabetic complications and antioxidant treatment can protect the target organs against diabetes.     

Relationship between the resistance to bile salts and low pH with exopolysaccharide (EPS) production of Bifidobacterium spp. isolated from infants feces and breast milk

The purpose of this study was to investigate a possible relation between resistance to bile salts and low pH with exopolysaccharide (EPS) producing of Bifidobacterium spp. In this study, a total of 31 Bifidobacterium spp. were isolated from breast fed infants feces and breast milk samples. As a result of the identification tests, isolates were identified as Bifidobacterium breve (15 strains), B. bifidum (11 strains), B. pseudocatenulatum (3 strains) and B. longum (2 strains). Bifidobacterium spp. were determined exopolysaccharide (EPS) production. EPS productions observed at chance rations (38.00–97.64 mg/l) among of Bifidobacterium spp. Furthermore, Bifidobacterium spp. were determined resistance to bile salts and low pH. Positive correlations between production of exopolysaccharide and resistance to bile salts (p < 0.01) or low pH (p < 0.01) were found Bifidobacterium spp. This investigation showed that high EPS production of Bifidobacteria may be important in the selection of probiotic strains for resistance to bile salts and low pH.     

Influence of knee osteoarthritis on exercise capacity and quality of life in obese adults

Objective: The objective was to determine whether knee osteoarthritis (OA) reduces exercise ambulatory capacity and impairs quality of life (QOL) in obese individuals. Research Methods and Procedures: There were 56 subjects, with and without knee OA, who were obese. The subjects were evaluated with anthropometric measurements, a body composition assessment, maximal cardiopulmonary exercise test, 6‐minute walk test (6‐MWT), perceived exertion (RPE), self‐reported disability [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)], and the Medical Outcomes Study Short Form 36 (SF‐36). Results: VO_2peak was significantly higher in the controls when compared with the patients (mean ± standard deviation, 1.584 ± 0.23 L/kg per min vs. 0.986 ± 0.20 L/kg per min; p < 0.001). Obese subjects without knee OA walked a significantly longer distance in the 6‐MWT than obese patients with knee OA (p < 0.001). We also observed significant negative correlation between Vo ₂max and RPE, WOMAC pain and physical limitation, and bodily pain and general health domains of short‐form 36. Discussion: Knee OA reduces exercise and ambulatory capacity and impairs QOL in obese individuals. RPE, WOMAC pain, and SF‐36 items might provide information about exercise capacity in the obese subjects with knee OA. Our study confirms that exercise capacity and QOL might be improved by energetic and intensive treatment of pain resulting from knee OA.