Flavone 5-O-glucosides from Daphne sericea

The aerial parts of Daphne sericea yielded two new flavonoids, luteolin 7-methyl ether 5-β-d-glucoside and luteolin 7,3′-dimethyl ether 5-β-d-glucoside, as well as luteolin 7-methyl ether, isovitexin, apigenin and its 7-β-d-glucoside.     

Two new neoflavonoids and C-glycosylflavones from Passiflora serratodigitata

The aerial parts of Passiflora serratodigitata yielded 5,7-dihydroxy-4-phenylcoumarin, its 7-β-glucoside and the known C-glycosylflavones 2″-xylosylvitexin, 2″-xylosylisovitexin, vitexin, isovitexin, a vicenin, and orientin. The known flavone chrysin was also isolated. This is the first report of neoflavonoids in the family Passifloraceae.     

Assessment of post-stroke elbow flexor spasticity in different forearm positions

Abstract

Purpose/Aim: There have been conflicting results regarding which muscle contribute most to the elbow spastic flexion deformity. This study aimed to investigate whether flexor spasticity of the elbow changed according to the position of the forearm, and to determine the muscle or muscles that contributed most to the elbow spastic flexion deformity by clinical examination.

Methods: This study is a single group, observational and cross-sectional study. Sixty patients were assessed for elbow flexor spasticity in different forearm positions (pronation, neutral and supination) with Modified Tardieu Scale. The primary outcome measure was a domain of the Modified Tardieu Scale, the dynamic component of spasticity (spasticity angle).

Results: In general, there was a significant difference between forearm positions regarding spasticity angle (p?<?.001). In pairwise comparisons, median spasticity angles in pronation (70 degrees) and neutral position (60 degrees) were significantly higher than those in supination (57.5 degrees) (adjusted p?<?.001 and adjusted p?=?.003, respectively). However, median spasticity angle in pronation did not differ significantly from those in neutral position in favour of pronation (adjusted p?=?.274).

Conclusions: The severity of spasticity changes according to the elbow position which suggests that the magnitude of contribution of each elbow flexor muscle to spastic elbow deformity is different. Reduction of spasticity from pronation to supination leads us to consider brachialis as the most spastic muscle. Since biceps was suggested to be the least spastic muscle in this study, and also to avoid spastic pronation deformity of the forearm, it should be rethought before performing chemodenervation into biceps muscle.     

Nitric oxide: a novel inducer for enhancement of microbial lipase production

The purpose of this study was to elucidate whether exogenous nitric oxide (NO) has a potential beneficial effect on lipase production capacity of some microorganisms. Sodium nitroprusside (SNP) was used as an exogenous NO donor in production medium. In comparison with the control (0 nM SNP), SNP concentrations from 10 to 100 nM induced lipase production in mesophilic bacterium Bacillus subtilis and cold-adapted yeast Yarrowia lipolytica. Especially, the maximum lipase activities for Y. lipolytica (81.2 U/L) and B. subtilis (74.5 U/L) were attained at 30 and 50 nM SNP concentrations, respectively. When compared to the control, the optimal SNP concentrations resulted in about 5.14 and 2.27-fold increases in lipase activities of B. subtilis and Y. lipolytica, respectively. Besides, it was found that the optimal SNP concentrations provided shorter incubation periods for lipase production. Conversely, no significant positive effect of exogenous NO on lipase production was determined for thermophilic bacterium Geobacillus stearothermophilus. This study showed for the first time that exogenous NO could be used as an inducer in the production of microbial lipases.     

In silico investigation of PARP-1 catalytic domains in holo and apo states for the design of high-affinity PARP-1 inhibitors

The rational design of high-affinity inhibitors of poly-ADP-ribose polymerase-1 (PARP-1) is at the heart of modern anti-cancer drug design. While relevance of enzyme to DNA repair processes in cellular environment is firmly established, the structural and functional understanding of the main determinants for high-affinity ligands controlling PARP-1 activity is still lacking. The conserved active site of PARP-1 represents an ideal target for inhibitors and may offer a novel target at the treatment of breast cancer. To fill the gap in the structural knowledge, we report on the combination of molecular dynamics (MD) simulations, principal component analysis (PCA), and conformational analysis that analyzes in great details novel binding mode for a number of inhibitors at the PARP-1. While optimization of the binding affinity for original target is an important goal in the drug design, many of the promising molecules for treatment of the breast cancer are plagued by significant cardiotoxicity. One of the most common side-effects reported for a number of polymerase inhibitors is its off-target interactions with cardiac ion channels and hERG1 channel, in particular. Thus, selected candidate PARP-1 inhibitors were also screened in silico at the central cavities of hERG1 potassium ion channel.     

8-Br-cADPR, a TRPM2 ion channel antagonist,inhibits renal ischemia–reperfusion injury

The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na⁺ and Ca ²⁺. The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia–reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1β, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia–reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.     

Expression of several growth factors and their receptor genes in human colon carcinomas

We have examined the expression of mRNAs for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-α), EGF receptor (EGFR), PDGF-A chain (PDGFA), PDGF-B chain (PDGFB) and PDGF receptor (PDGFR) genes in seven human colorectal carcinoma cell lines and 18 human colorectal carcinomas. In surgically resected specimens of the 18 colorectal tumors, TGF-α, EGFR, PDGFA, PDGFB and PDGFR mRNAs were detected at various levels in 15 (83%), 9 (50%), 18 (100%), 8 (44%) and 12 (67%), respectively. They were also detected in normal tissues. Interestingly, EGF mRNA was detected in only five (28%) of the tumors, but not in normal mucosa. Expression of EGF was also confirmed immunohistochemically in tumor cells. Of the five tumors expressing EGF, four expressed EGFR mRNA and showed a tendency to invade veins and lymphatics. All the colorectal carcinoma cell lines expressed TGF-α mRNA, and five cell lines expressed EGFR mRNA simultaneously. Production of TGF-α protein by DLD-1 and CoLo320DM cells was confirmed by TGF-α specific monoclonal antibody binding assay. The spontaneous³H-thymidine uptake by DLD-1 was suppressed by an anti-TGF-α monoclonal antibody. PDGFA and PDGFB mRNA were also expressed in four cell lines, but PDGFR and EGF mRNA was not detected. These results suggest that human colorectal carcinomas express multi-loops of growth factors and that TGF-α produced by tumor cells functions as an autocrine growth factor in human colonic carcinoma.     

The Effects of Chromium Histidinate on Mineral Status of Serum and Tissue in Fat-Fed and Streptozotocin-Treated Type II Diabetic Rats

The present study was conducted to investigate the effects of chromium histidinate (CrHis) against experimentally induced type II diabetes and on chromium (Cr), zinc (Zn), selenium (Se), manganese (Mn), iron (Fe), and copper (Cu) in serum, liver, and kidney of diabetic rats. The male Wistar rats (n = 60, 8 weeks old) were divided into four groups. Group I received a standard diet (12% of calories as fat); group II were fed standard diet and received CrHis (110 mcg CrHis/kg body weight per day); group III received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg i.p.; HFD/STZ); group IV were treated as group III (HFD/STZ) but supplemented with 110 mcg CrHis/kg body weight per day. The mineral concentrations in the serum and tissue were determined by atomic absorption spectrometry. Compared to the HFD/STZ group, CrHis significantly increased body weight and reduced blood glucose in diabetic rats (p < 0.001). Concentrations of Cr, Zn, Se, and Mn in serum, liver, and kidney of the diabetic rats were significantly lower than in the control rats (p < 0.0001). In contrast, higher Fe and Cu levels were found in serum and tissues from diabetic versus the non-diabetic rats (p < 0.001). Chromium histidinate supplementation increased serum, liver, and kidney concentrations of Cr and Zn both in diabetic and non-diabetic rats (p < 0.001). Chromium supplementation increased Mn and Se levels in diabetic rats (p < 0.001); however, it decreased Cu levels in STZ-treated group (p < 0.001). Chromium histidinate supplementation did not affect Fe levels in both groups (p > 0.05). The results of the present study conclude that supplementing Cr to the diet of diabetic rats influences serum and tissue Cr, Zn, Se, Mn, and Cu concentrations.     

Effect of Diplocystis tipulae Sherlock (Eugregarinida: Apicomplexa), a coelomic gregarine pathogen of tipulids, on the larval size of Tipula paludosa Meigen (Tipulidae: Diptera)

This study demonstrates the debilitative effect of a coelomic gregarine, Diplocystis tipulae, on Tipula paludosa. The larvae were provided contaminated fresh grass leaves from a field where 40.0% of T. paludosa larvae were infected by this pathogen. Resultant infected larvae were separated into four groups according to infection level. Analysing their weights, lengths, and weight/length ratios showed that larval size decreased as infection level increased. Differences, especially at the lower and upper levels of the infection levels, were statistically significant. It was concluded that infection by D. tipulae affected the size of T. paludosa larvae resulting in smaller individuals.     

Trace Elements in Obese Turkish Children

The quality of the diet of obese children is poor. Eating habits may alter micronutrient status in obese patients. In this study, we determined the serum levels of selenium, zinc, vanadium, molybdenum, iron, copper, beryllium, boron, chromium, manganese, cobalt, silver, barium, aluminum, nickel, cadmium, mercury, and lead in obese Turkish children. Thirty-four obese and 33 healthy control subjects were enrolled in the study. Serum vanadium and cobalt levels of obese children were significantly lower than those of the control group (0.244 ± 0.0179 vs. 0.261 ± 0.012 μg/l, p < 0.001, and 0.14 ± 0.13 vs. 0.24 ± 0.15 μg/l, p = 0.011, respectively). There was no significant difference between groups regarding the other serum trace element levels. In conclusion, there may be alterations in the serum levels of trace elements in obese children and these alterations may have a role in the pathogenesis of obesity.