Effect of Lycopene Application in Rats with Experimental Diabetes Using Lipoprotein, Paraoxonase and Cytokines

This study was conducted with the purpose of researching the effect of lycopene application on lipoprotein, paraoxonase (PON) and cytokines that are projected to be used in the diagnosis and treatment of diabetes by making experimental diabetes. At the end of a 1-month trial period, under ether anesthesia with jelly tubes, blood samples were taken from rat hearts. Blood samples were centrifuged and serum was obtained. From the serum samples, HbA_1c, paraoxonase activity, lipoprotein levels and cytokines were determined. HbA_1c levels and PON activity were found to be p < 0.001. At the triglyceride level, with regard to the control group, in all the groups a significant rise occurred (p ≤ 0.001). At the cholesterol level, with regard to the control group, a decline was observed in the other groups (p < 0.05). At the VLDL level, with regard to the control group, a significant rise was observed in the other groups (p < 0.05). At the HDL (p < 0.001) and LDL (p < 0.05) levels, with regard to the control group, a significant decline was observed in the other groups. At the TNF-α, IL-2, IL-6 and IL-10 levels no difference was found (p > 0.05). Experimental diabetes models have an important place in analyzing diabetes complications and determining treatment approaches.     

Evaluation of Essential and Toxic Trace Elements in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Pseudoexfoliation syndrome (PEX), an age-related disorder of the eye, is associated with significant ophthalmic morbidity and can lead to pseudoexfoliation glaucoma (PEG). The etiology of this disorder has not been clearly understood. Trace elements have been suggested to have roles in the pathogenesis of several disorders. This study aimed to determine whether trace element levels have a role in the development of PEX and/or PEG. Levels of zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), chromium (Cr), cobalt (Co), molybdenum (Mo), nickel (Ni), vanadium (V), arsenic (As), aluminum (Al), mercury (Hg), cadmium (Cd), and strontium (Sr) were determined in serum samples of 32 cases of PEX, 30 cases of PEG, and 32 control subjects using inductively coupled plasma–mass spectrometry. Mn, Mo, and Hg concentrations were found to be significantly increased in patients with PEX. Logistic regression revealed Mn and Hg as the strongest determinants of PEX and Mo as the strongest determinant of PEG in the studied Turkish subjects. Levels of Mn, Cr, Co, Mo, Al, Hg, Sr, Ni, V, and As were determined for the first time in these ophthalmological disorders. Increased levels of serum Mn, Mo, and Hg suggest a possible role of these elements in the pathobiology of PEX.     

Anticarcinogenic effects of halofuginone on lung‐derived cancer cells

Malignant mesothelioma is a rare but aggressive form of malignancy, which is difficult to diagnose and is resistant to current chemotherapeutic treatment options. Molecular techniques have been used to investigate the mechanisms of action and the beneficial therapeutic effects of halofuginone (HF) in several cancers but not malignant mesotheliomas. In this study, the antiproliferative and apoptotic effects of HF were investigated through its ability to deregulate EGFR downstream signalling cascade proteins in the pathologically aggressive malignant mesothelioma and non‐small‐cell lung cancer cells. We showed that administration of HF at nanomolar concentrations induced a dose‐dependent reduction in the viability of cancer cells, made cell cycle arrest, inhibited proliferation of cancer cells via STAT3 and ERK1/2 pathways and triggered the apoptotic cascade via p38MAPK. We demonstrated that the apoptotic cell death mechanism was mediated by enhanced activation of caspase‐3 and concomitant PARP cleavage, downregulation of Bcl‐2 and upregulation of Bax in both malignant mesothelioma and lung cancer cells. In particular, we demonstrated that cancer cells were more sensitive to HF treatment than normal mesothelial cells. Taken together, this study suggests that HF exerts its anticancer effects in lung‐derived cancers by targeting signal transduction pathways mainly through deregulation of ERK1/2, STAT3 and p38MAPK to reduce cancer cell viability, induce cell cycle arrest and apoptotic cell death. Thus, HF might be considered as a potential agent against malignant mesothelioma and/or lung cancer cells.     

Improved nitrogen nutrition enhances root uptake, root-to-shoot translocation and remobilization of zinc ((65) Zn) in wheat

This study focussed on the effect of increasing nitrogen (N) supply on root uptake and root-to-shoot translocation of zinc (Zn) as well as retranslocation of foliar-applied Zn in durum wheat (Triticum durum). Nutrient solution experiments were conducted to examine the root uptake and root-to-shoot translocation of (65) Zn in seedlings precultured with different N supplies. In additional experiments, the effect of varied N nutrition on retranslocation of foliar-applied (65) Zn was tested at both the vegetative and generative stages. When N supply was increased, the (65) Zn uptake by roots was enhanced by up to threefold and the (65) Zn translocation from roots to shoots increased by up to eightfold, while plant growth was affected to a much smaller degree. Retranslocation of (65) Zn from old into young leaves and from flag leaves to grains also showed marked positive responses to increasing N supply. The results demonstrate that the N-nutritional status of wheat affects major steps in the route of Zn from the growth medium to the grain, including its uptake, xylem transport and remobilization via phloem. Thus, N is a critical player in the uptake and accumulation of Zn in plants, which deserves special attention in biofortification of food crops with Zn.     

Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling

Spred/Sprouty family proteins negatively regulate growth factor-induced ERK activation. Although the individual physiological roles of Spred-1 and Spred-2 have been investigated using gene-disrupted mice, the overlapping functions of Spred-1 and Spred-2 have not been clarified. Here, we demonstrate that the deletion of both Spred-1 and Spred-2 resulted in embryonic lethality at embryonic days 12.5 to 15.5 with marked subcutaneous hemorrhage, edema, and dilated lymphatic vessels filled with erythrocytes. This phenotype resembled that of Syk^−/− and SLP-76^−/− mice with defects in the separation of lymphatic vessels from blood vessels. The number of LYVE-1-positive lymphatic vessels and lymphatic endothelial cells increased markedly in Spred-1/2-deficient embryos compared with WT embryos, while the number of blood vessels was not different. Ex vivo colony assay revealed that Spred-1/2 suppressed lymphatic endothelial cell proliferation and/or differentiation. In cultured cells, the overexpression of Spred-1 or Spred-2 strongly suppressed vascular endothelial growth factor-C (VEGF-C)/VEGF receptor (VEGFR)-3-mediated ERK activation, while Spred-1/2-deficient cells were extremely sensitive to VEGFR-3 signaling. These data suggest that Spreds play an important role in lymphatic vessel development by negatively regulating VEGF-C/VEGFR-3 signaling.     

Studies on the antioxidant activities of some new chromone compounds

Recent reviews evidence that the naturally occurring compounds containing the chromone skeleton exhibit antiradical activities, providing protection against oxidative stress. The antioxidant activities of 13 new synthesized chromonyl‐2,4‐thiazolidinediones, chromonyl‐2,4‐imidazolidinediones and chromonyl‐2‐thioxoimidzolidine‐4‐ones were evaluated using in vitro antioxidant assays, including superoxide anion radical (), hydroxyl radical (), 2,2‐diphenyl‐1‐picryl‐hydrazyl free radical (DPPH^?) scavenging capacity and total antioxidant capacity ferric ion reducing activity. Superoxide anion radical was produced using potassium superoxide/18‐crown‐6‐ether dissolved in dimethylsulfoxide, and the Fenton‐like reaction (Fe(II) + H₂O₂) was a generator of hydroxyl radicals. Chemiluminescence, spectrophotometry, electron paramagnetic resonance (EPR) and 5,5‐dimethyl‐1‐pyrroline‐N‐oxide (DMPO) as the spin trap were the measurement techniques. The results showed that the majority of the chromone derivatives tested showed a strong scavenging effect towards free radicals, similar to the chemiluminescence reaction with superoxide anion radical with a high activity, inhibition of the DMPO‐OOH radical EPR signal (24–58%), the DMPO‐OH radical EPR signal (4–75%) and DPPH radical EPR signal (6–100%) at 1 mmol/L. Several of the examined compounds exhibited the high reduction potentials. The results obtained show that the new synthesized chromone derivatives may directly scavenger reactive oxygen species and thus may play a protective role against oxidative damage. Copyright © 2014 John Wiley & Sons, Ltd.     

Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures.     

Localization of pan-cadherin immunoreactivity in adult rat tissues

Cadherins, being responsible for selective cell recognition and normal tissue integrity in adults, regulate morphogenesis in a variety of organs during development. In this study, anti-rat pan-cadherin antibody, specific to all subgroups of the cadherin family, was used to map the distribution of the pan-cadherin immunoreactivity in adult rat organs. Pan-cadherin immunoreactivity positive tissues were: secretory cells of the adenohypophysis, autonomic nerve, corneal epithelium, oesophageal nerve plexus, stomach and pyloric glandular cells, epithelium of the ileum and its nerve plexus, alveolar cells of the lung, proximal convoluted tubules of the kidney, islet cells of Langerhans, and the acinar cells of the exocrine pancreas. For the first time, positive pan-cadherin immunoreactivity was demonstrated in the epithelial cells of the corpus ciliaris and in the nerve plexus of corpus cavernosum of the penis. In conclusion, our results suggest that cells in many tissues and organs of the adult rat synthesize cadherins.     

Marker utility of miniature inverted-repeat transposable elements for wheat biodiversity and evolution

Transposable elements (TEs) account for up to 80% of the wheat genome and are considered one of the main drivers of wheat genome evolution. However, the contribution of TEs to the divergence and evolution of wheat genomes is not fully understood. In this study, we have developed 55 miniature inverted-repeat transposable element (MITE) markers that are based on the presence/absence of an element, with over 60% of these 55 MITE insertions associated with wheat genes. We then applied these markers to assess genetic diversity among Triticum and Aegilops species, including diploid (AA, BB and DD genomes), tetraploid (BBAA genome) and hexaploid (BBAADD genome) species. While 18.2% of the MITE markers showed similar insertions in all species indicating that those are fossil insertions, 81.8% of the markers showed polymorphic insertions among species, subspecies, and accessions. Furthermore, a phylogenetic analysis based on MITE markers revealed that species were clustered based on genus, genome composition, and ploidy level, while 47.13% genetic divergence was observed between the two main clusters, diploids versus polyploids. In addition, we provide evidence for MITE dynamics in wild emmer populations. The use of MITEs as evolutionary markers might shed more light on the origin of the B-genome of polyploid wheat.     

Immunohistochemical characterization of perineal melanoma in Kilis goats

We describe the clinical, histopathological and immunohistochemical features of the malignant melanomas in the perineal regions of Kilis goats from Sanliurfa province in Turkey. We studied 13 female Kilis goats between 3 and 8 years old that were brought to Harran University Veterinary School, Department of Surgery, between 2002 and 2010. By macroscopic examination, the masses were determined to have elastic consistency, dark brown-black color, necrotic surfaces and ulceration. Microscopically, pleomorphic cells were observed under the basal layer and these advanced toward the dermis. These cells were polyhedral, round or spindle-shaped, anaplastic, and their cytoplasm contained varying amounts of dark brown-black pigments. Immunohistochemical staining was obtained with anti-melan A, vimentin and S100 antibodies.