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21.
Protective effects of flavonoids and two metabolites against oxidative stress in neuronal PC12 cells
AimsRecent interest has focused on plant antioxidants as potentially useful neuroprotective agents. In most studies only the genuine forms of flavonoids were used, although they are rapidly metabolized. Therefore, we have compared protective activities of two flavonoids (luteolin, quercetin) and two of their bioavailable metabolites (3,4-DHPAA and 3,4-DHT) against oxidative stress, induced by peroxides (t-BHP, H2O2) and iron (FeSO4), in neuronal PC12 cells.Main methodsWe have measured their effect on the prevention of cell death (MTT assay), glutathione depletion (GSH assay), lipid peroxidation (MDA assay) and production of ROS (DCF assay). Differentiated PC12 cells were used as a model system of neuronal cells. The compounds (concentration range 6–25 µmol/L) were tested in preincubation and coincubation experiments.Key findingsIn MTT and DCF assays all tested compounds showed excellent protection. When cells were exposed to peroxides, both metabolites increased GSH levels less efficiently than their parent flavonoids in both types of incubations. Following exposure to iron, only coincubation significantly prevented GSH depletion and the metabolites surprisingly mimicked the suppressive effect of flavonoids. MDA levels induced by all stressors were reduced more potently during coincubation than during preincubation with polyphenols. While the lipophilic metabolite 3,4-DHT exerted excellent antilipoperoxidant activity, the hydrophilic metabolite 3,4-DHPAA was less effective.SignificanceThese results demonstrate that most of the protective effects of flavonoids against oxidative stress in PC12 cells are continued despite biodegradation of the parent flavonoids. In general, the lipophilic metabolite 3,4-DHT was more active than the hydrophilic 3,4-DHPAA. 相似文献
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In the 1975-2004 period, 130 cases of pterygium were estimated, 83 males and 47 females, on a small island Rab. Island Rab is located in the north part of the Adriatic sea, which has very high index of sun radiation. Pterygium is usually histopathologically defined as a hyperplasia of conjunctival tissue, elastoid degeneration of subepithelieum and fragmentation of Bowman's membrane. Our histopathological findings in 73 eyes are following: conjunctiva with neovascularisation, leukocyte margination and subepithelial basophilic degeneration, proliferation of conjunctival tissue, acanthosis and squamous metaplasia, and mucinous elements, focaly present plasma cells, focuses of increased pigmentisation in basal epithelial layers, tenon capsule with edema, diffuse neovascularisation and fragmentation of fibrils. These findings suggest that in severe cases of pterygium histopathologically exists precancerosis. In conclusion, on the basis of these histopathological findings, especially in the Tenon capsule, we suggest that for surgical procedure of pterygium the excision of the Tenon capsule, extensively under pterygium, is necessary. 相似文献
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Vojniković B Njirić S Coklo M Toth I Spanjol J Marinović M 《Collegium antropologicum》2007,31(Z1):61-62
The aim of this epidemiologic study, on small island Rab, in North Adriatic Sea, is to estimate correlation between climatic factors, specially chronic exposure to strong visible and UV light, and appearance of pterygium and exfoliation syndrome. In the first group of population which live in a village and who are agriculturists and fishermen (480 persons) appearance of pterygium is in 23% (16% in males and 7% in females), but 0.0% in urban people (61 people). The appearance of exfoliation syndrome was in the first group of agriculturists and fishermen population in 21%, of which 19% of males and 2% of females, and in urban people 0.0%. The higher intraocular pressure in exfoliation syndrome was 92%. All population in this examination were in the highest age (mean age is 65-80 years). Chronic exposure to sunlight caused the high percentage appearance of pterygium and exfoliation syndrome. 相似文献
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Veljkovic V Mouscadet JF Veljkovic N Glisic S Debyser Z 《Bioorganic & medicinal chemistry letters》2007,17(5):1226-1232
Flavonoid compounds represent an important natural source of antiretrovirals for AIDS therapy due to their significant anti-HIV-1 activity and low toxicity. Here we propose a simple theoretical criterion to discriminate active from inactive flavonoids that is suitable for rapid in silico screening of flavonoid libraries, and selection and optimization of lead compounds with anti-HIV-1 activity. 相似文献
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Sanja Antic Michael T. Wolfinger Anna Skucha Stefanie Hosiner Silke Dorner 《Molecular and cellular biology》2015,35(13):2309-2320
The translation and degradation of mRNAs are two key steps in gene expression that are highly regulated and targeted by many factors, including microRNAs (miRNAs). While it is well established that translation and mRNA degradation are tightly coupled, it is still not entirely clear where in the cell mRNA degradation takes place. In this study, we investigated the possibility of mRNA degradation on the ribosome in Drosophila cells. Using polysome profiles and ribosome affinity purification, we could demonstrate the copurification of various deadenylation and decapping factors with ribosome complexes. Also, AGO1 and GW182, two key factors in the miRNA-mediated mRNA degradation pathway, were associated with ribosome complexes. Their copurification was dependent on intact mRNAs, suggesting the association of these factors with the mRNA rather than the ribosome itself. Furthermore, we isolated decapped mRNA degradation intermediates from ribosome complexes and performed high-throughput sequencing analysis. Interestingly, 93% of the decapped mRNA fragments (approximately 12,000) could be detected at the same relative abundance on ribosome complexes and in cell lysates. In summary, our findings strongly indicate the association of the majority of bulk mRNAs as well as mRNAs targeted by miRNAs with the ribosome during their degradation. 相似文献
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Sanja Cicko Melanie Grimm Korcan Ayata Jessica Beckert Anja Meyer Madelon Hossfeld Gernot Zissel Marco Idzko Tobias Müller 《Respiratory research》2015,16(1)
Rationale
Pulmonary fibrosis is a progressive disease with only few treatment options available at the moment. Recently, the nucleoside uridine has been shown to exert anti-inflammatory effects in different animal models, e.g. in acute lung injury or bronchial asthma.Method
Therefore, we investigated the influence of uridine supplementation on inflammation and fibrosis in the classical bleomycin model. Male C57BL/6 mice received an intratracheal injection of bleomycin on day 0 and were treated intraperitoneally with uridine or vehicle. The degree of inflammation and fibrosis was assessed at different time points.Results
Uridine administration resulted in attenuated inflammation, as demonstrated by reduced leukocytes and pro-inflammatory cytokines in the broncho-alveolar lavage (BAL) fluid. Furthermore, collagen deposition in the lung interstitium was also reduced by uridine supplementation. Similar results were obtained in a model in which animals received repeated intraperitoneal bleomycin injections. In addition uridine inhibited collagen and TGF-ß synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils.Conclusion
In summary, we were able to show that uridine has potent anti-inflammatory and anti-fibrotic properties. As uridine supplementation has been shown to be well tolerated and safe in humans, this might be a new therapeutic approach for the treatment of fibrotic lung diseases. 相似文献29.
Sanja?Nedic Steven?M.?Stufflebeam Carlo?Rondinoni Tonicarlo?R.?Velasco Antonio?C.?dos Santos Joao?P.?Leite Ana?C.?Gargaro Lilianne?R.?Mujica-ParodiEmail author Jaime?S.?IdeEmail author 《BMC neurology》2015,15(1):262
Background
Epilepsy is one of the most prevalent neurological disorders. It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Existing fMRI literature points to widespread network disturbances in functional connectivity. Per previous scalp and intracranial EEG studies and consistent with excessive local synchronization during interictal discharges, we hypothesized that, relative to same regions in healthy controls, epileptogenic foci would exhibit less chaotic dynamics, identifiable via entropic analyses of resting state fMRI time series.Methods
In order to first validate this hypothesis on a cohort of patients with known ground truth, here we test individuals with well-defined epileptogenic foci (left mesial temporal lobe epilepsy). We analyzed voxel-wise resting-state fMRI time-series using the autocorrelation function (ACF), an entropic measure of regulation and feedback, and performed follow-up seed-to-voxel functional connectivity analysis. Disruptions in connectivity of the region exhibiting abnormal dynamics were examined in relation to duration of epilepsy and patients’ cognitive performance using a delayed verbal memory recall task.Results
ACF analysis revealed constrained (less chaotic) functional dynamics in left temporal lobe epilepsy patients, primarily localized to ipsilateral temporal pole, proximal to presumed focal points. Autocorrelation decay rates differentiated, with 100 % accuracy, between patients and healthy controls on a subject-by-subject basis within a leave-one-subject out classification framework. Regions identified via ACF analysis formed a less efficient network in patients, as compared to controls. Constrained dynamics were linked with locally increased and long-range decreased connectivity that, in turn, correlated significantly with impaired memory (local left temporal connectivity) and epilepsy duration (left temporal – posterior cingulate cortex connectivity).Conclusions
Our current results suggest that data driven functional MRI methods that target network dynamics hold promise in providing clinically valuable tools for identification of epileptic regions.30.