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排序方式: 共有298条查询结果,搜索用时 15 毫秒
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Aleksandra Topic Marina Milenkovic Snezana Uskokovic-Markovic Dragana Vucicevic 《Biological trace element research》2010,134(3):296-306
Investigations of effective, orally active, and safe antidiabetic metallopharmaceuticals have been carried out during the
last two decades. It has been reported that tungsten compounds mimic the action of insulin in intact cell systems. As insulin
mimetics, the most investigated tungsten compound was sodium tungstate (ST), rarely investigated was tungstophosphoric acid
(WPA), but never alanine complex of tungstophosphoric acid (WPA-A). In this study, the insulin mimetic activity of three different
tungsten compounds, ST, WPA, and WPA-A, was evaluated by means of in vitro measurements of the glucose uptake and inhibition
of free fatty acids release from epinephrine-treated isolated rat white adipocytes. We investigated the influence of concentration
(lower and higher, 0.1 and 1.0 mM, respectively) and solvent: isotonic salt solution—saline (0.9% w/v of NaCl) and dimethyl sulfoxide (DMSO; 2% v/v), on the biological effect of tested compounds. Our experimental data showed that all of the three investigated tungsten
compounds possess insulin mimetic activity in vitro on the isolated adipocytes. Influence of concentration and solvents on
insulin mimetic effect for the certain tungsten compounds were: WPA was shown effect independently of concentration and solvents;
higher concentration and DMSO were significant decreasing insulin mimetic effect of ST; lower concentration and saline led
to decreasing effect of WPA-A. Generally, there were no differences in insulin mimetic effect of three tungsten compounds
in lower concentration and dissolved in DMSO. When saline was used as solvent, it was needed higher concentration of investigated
compounds to accomplish the same effect. In conclusion, our results suggest that low concentration (0.1 mM) of ST, WPA, and
WPA-A dissolved in 2% DMSO could be the good candidates for in vivo investigation of their antidiabetic properties. 相似文献
3.
Ljiljana Vapa Mihajla Djan Dragana Obreht Milos Beukovic Milan Vapa 《European Journal of Wildlife Research》2007,53(1):52-54
The pheasant breeds are widely used for restocking of natural populations depleted by hunting. The pheasant population number
decline was detected during the 1970s in many hunting areas of Europe. One of its possible reasons might be the loss of adaptability
in populations originating from breeding stations, which was caused by inbreeding depression. The aim of this paper was the
analysis of genetic variability in pheasant populations from three breeding stations in Vojvodina province (Serbia) by means
of allozyme diversity detection. The allozyme variability analysis of pheasants from all three breeding stations revealed
polymorphisms at nine loci: Ldh-1, Mor-1, Mor-2, Es-1, Mod-2, Pgd, Gpi-2, Odh, and Sod. The analysis of individuals from three different breeding stations showed mean values of observed heterozygosity of H
o=0.137, polymorphism P
95%=30%, and H/P ratio H/P=0.430, which indicate a normal level of genetic variability for bird populations. Comparative analysis of three pheasant
populations showed a high level of interpopulation differentiation. 相似文献
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Christina Brennenstuhl Naoyuki Tanimoto Markus Burkard Rebecca Wagner Sylvia Bolz Dragana Trifunovic Clement Kabagema-Bilan Francois Paquet-Durand Susanne C. Beck Gesine Huber Mathias W. Seeliger Peter Ruth Bernd Wissinger Robert Lukowski 《The Journal of biological chemistry》2015,290(16):10242-10255
Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in the visual transduction cascade in rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. the degradation of cyclic guanosine-3′,5′-monophosphate at specifically tuned rates and kinetics. Recently, the human PDE6H gene was identified as a novel locus for autosomal recessive (incomplete) color blindness. However, the three different classes of cones were not affected to the same extent. Short wave cone function was more preserved than middle and long wave cone function indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unknown mechanism. To study normal and disease-related functions of cone Pde6h in vivo, we generated Pde6h knock-out (Pde6h−/−) mice. Expression of PDE6H in murine eyes was restricted to both outer segments and synaptic terminals of short and long/middle cone photoreceptors, whereas Pde6h−/− retinae remained PDE6H-negative. Combined in vivo assessment of retinal morphology with histomorphological analyses revealed a normal overall integrity of the retinal organization and an unaltered distribution of the different cone photoreceptor subtypes upon Pde6h ablation. In contrast to human patients, our electroretinographic examinations of Pde6h−/− mice suggest no defects in cone/rod-driven retinal signaling and therefore preserved visual functions. To this end, we were able to demonstrate the presence of rod PDE6G in cones indicating functional substitution of PDE6. The disparities between human and murine phenotypes caused by mutant Pde6h/PDE6H suggest species-to-species differences in the vulnerability of biochemical and neurosensory pathways of the visual signal transduction system. 相似文献
6.
Blanca Arango-Gonzalez Dragana Trifunovi? Ayse Sahaboglu Katharina Kranz Stylianos Michalakis Pietro Farinelli Susanne Koch Fred Koch Sandra Cottet Ulrike Janssen-Bienhold Karin Dedek Martin Biel Eberhart Zrenner Thomas Euler Per Ekstr?m Marius Ueffing Fran?ois Paquet-Durand 《PloS one》2014,9(11)
Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement of alternative cell death mechanisms in neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups of hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H, Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for different forms of cell death. We show that apoptosis plays only a minor role in the inherited forms of retinal neurodegeneration studied, where instead, a non-apoptotic degenerative mechanism common to all mutants is of major importance. Hallmark features of this pathway are activation of histone deacetylase, poly-ADP-ribose-polymerase, and calpain, as well as accumulation of cyclic guanosine monophosphate and poly-ADP-ribose. Our work thus demonstrates the prevalence of alternative cell death mechanisms in inherited retinal degeneration and provides a rational basis for the design of mutation-independent treatments. 相似文献
7.
Many bacterial pathogens that cause different illnesses employ the cytolethal distending toxin (CDT) to induce host cell DNA damage, leading to cell cycle arrest or apoptosis. CDT is a tripartite holotoxin that consists of a DNase I family nuclease (CdtB) bound to two ricin-like lectin domains (CdtA and CdtC). Through the use of structure-based mutagenesis, biochemical and cellular toxicity assays, we have examined several key structural elements of the CdtA and CdtC subunits for their importance to toxin assembly, cell surface binding, and activity. CdtA and CdtC possess N- and C-terminal nonglobular polypeptides that extensively interact with each other and CdtB, and we have determined the contribution of each to toxin stability and activity. We have also functionally characterized two key binding elements of the holotoxin revealed from its crystal structure. One is an aromatic cluster in CdtA, and the other is a long and deep groove that is formed at the interface of CdtA and CdtC. We demonstrate that mutations of the aromatic patch or groove residues impair toxin binding to HeLa cells and that cell surface binding is tightly correlated with intoxication of cultured cells. These results establish several structure-based hypotheses for the assembly and function of this toxin family. 相似文献
8.
9.
Contassot E Jankovic D Schuler P Preynat-Seauve O Gehrke S Kerl K Beermann F French LE 《Pigment cell & melanoma research》2012,25(2):275-278
The incidence of melanoma has significantly increased, and a better understanding of its pathogenesis and development of new therapeutic strategies are urgently needed. Here, we describe a murine model of metastatic cutaneous melanoma using C57BL/6 mice expressing a mutated human N-Ras gene under the control of a tyrosinase promoter (TyrRas). These mice were topically exposed to 7,12- dimethylbenzanthracene (DMBA) for brief exposure periods. Cutaneous melanoma developed at the site of exposure on average by 19 weeks of age and in 80% of mice. Importantly, as in humans, melanoma development was associated with subsequent metastasis to tumor-draining lymph nodes. Critically, such metastatic behavior is transplantable, as intradermal inoculation of melanoma cells from TyrRas-DMBA mice into non-transgenic mice led to the growth of melanoma and, again, metastasis to skin-draining lymph nodes. This metastatic melanoma model closely mimics human pathology and should be a useful tool for studying melanoma pathogenesis and developing new therapies. 相似文献
10.
Antonella Marino Gammazza Manfredi Rizzo Roberto Citarrella Francesca Rappa Claudia Campanella Fabio Bucchieri Angelo Patti Dragana Nikolic Daniela Cabibi Giandomenico Amico Pier Giulio Conaldi Pier Luigi San Biagio Giuseppe Montalto Felicia Farina Giovanni Zummo Everly Conway de Macario Alberto J. L. Macario Francesco Cappello 《Cell stress & chaperones》2014,19(3):343-353
The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism. 相似文献