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91.
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The alleviative effects of two antioxidants, carnosine (Car) and melatonin (Mel), against titanium dioxide nanoparticles (TiO2‐NPs) toxicity‐induced oxidative and inflammatory renal damage were examined in rats. Administration of these antioxidants along with TiO2‐NPs effectively reduced serum urea, uric acid, creatinine, glucose, tumor necrosis factor‐α, interleukin‐6, C‐reactive protein, immunoglobulin G, vascular endothelial growth factor, and nitric oxide, as well as a significant amelioration of the decrease in glutathione levels in renal tissue was observed, compared to those in rats treated with TiO2‐NPs alone. The renoprotective properties of the antioxidants were confirmed by reduced intensity of renal damage as demonstrated by histological findings. In conclusion, Car and Mel play protective roles against TiO2‐NPs‐induced renal inflammation and oxidative injury, likely due to their antioxidant and anti‐inflammatory properties.  相似文献   
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Background

The resistance of melanoma cells to cisplatin restricts its clinical use. Therefore, the search for novel tumor inhibitors and effective combination treatments that sensitize tumor cells to this drug are still needed. We purified macrovipecetin, a novel heterodimeric C-type lectin, from Macrovipera lebetina snake venom and investigated its anti-tumoral effect on its own or combined with cisplatin, in human melanoma cells.

Methods

Biochemical characterization, in vitro cells assays such as viability, apoptosis, adhesion, migration, invasion, Western blotting and in silico analysis were used in this study.

Results

Macrovipecetin decreased melanoma cell viability 100 times more than cisplatin. Interestingly, when combined with the drug, macrovipecetin enhanced the sensitivity of SK-MEL-28 cells by augmenting their apoptosis through increased expression of the apoptosis inducing factor (AIF) and activation of ERK1/2, p38, AKT and NF-κB. Moreover, macrovipecetin alone or combined with cisplatin induced the expression of TRADD, p53, Bax, Bim and Bad and down-regulated the Bcl-2 expression and ROS levels in SK-MEL-28 cells. Interestingly, these treatments impaired SK-MEL-28 cell adhesion, migration and invasion through modulating the function and expression of αvβ3 integrin along with regulating E-cadherin, vimentin, β-catenin, c-Src and RhoA expression. In silico study suggested that only the α chain of macrovipecetin interacts with a region overlapping the RGD motif binding site on this integrin.

Conclusions

We validated the antitumor effect of macrovipecetin when combined, or not, with cisplatin on SK-MEL-28 cells.

General significance

The presented work proposes the potential use of macrovipecetin and cisplatin in combination as an effective anti-melanoma treatment.  相似文献   
96.
 Normal peripheral blood mononuclear cells (PBMC responders) were cultured together with non-irradiated allogeneic PBMC (more than 95% leukaemia blasts) derived from patients with acute leukaemia (referred to as leukaemic PBMC stimulators). Cytokine secretion was determined as cytokine concentrations in supernatants. Both normal PBMC and enriched CD4+ and CD8+ T cells responded to allostimulation with interferon (IFNγ) secretion. Interleukin-1 (IL-1) receptor antagonist and IL-2-neutralizing antibodies decreased IFNγ secretion. Exogenous IL-1β, IL-2 and IL-7 increased allostimulated IFNγ secretion, whereas decreased levels were seen in the presence of IL-6, IL-10 and granulocyte-colony-stimulating factor (G-CSF). During allorecognition IFNγ -neutralizing antibodies decreased acute myelogenous leukaemia (AML) blast secretion of G-CSF. We conclude that (i) both CD4+ and CD8+ T cells show allostimulated cytokine secretion in response to allogeneic stimulator cells containing a dominating population of native, cytokine-secreting leukaemia blasts, and (ii) IFNγ released during this response can modulate the function of allogeneic AML blasts. Received: 4 June 1996 / Accepted: 15 October 1996  相似文献   
97.
During foraging, leaf-cutting ant workers of different size classes perform various tasks along foraging trails. Commonly, small workers called hitchhikers climb on leaf fragments imposing an extra transport cost, so their presence is thought to reduce the individual foraging performance. There are four main hypotheses which may explain the occurrence of hitchhikers and a different behavioral act related to their role can be predicted for each. Hitchhiker behavior was observed considering these hypotheses and the effect of the hitchhikers on the walking speed and transport rate of foragers was evaluated. The behavioral registers were obtained from 1371 hitchhikers on foraging trails of Acromyrmex subterraneus subterraneus nests in the field. To verify the influence of hitchhikers on walking speed and transport rate, 239 foragers with hitchhikers and 250 foragers transporting only leaf fragments were analyzed. The walking speed, burden and transport rate of each forager were calculated. Data indicated not only that hitchhikers are vigilant but that they remain motionless on the leaf fragment probably in order to reduce the impact of their presence for the loaded forager. The impact of their presence is verified through walking speed reduction but as they ride preferentially on larger workers who transport larger leaf fragments, there are no losses in the individual transport rate. The transporter selection made by the hitchhiker ensures at the same time enhanced protection against phorid parasitoids and the maintenance of the leaf transport rate.  相似文献   
98.
Prior ecological research has shown that spatial processes can enhance the temporal stability of populations in fluctuating environments. Less explored is the effect of dispersal on rapid adaptation and its concomitant impact on population dynamics. For asexually reproducing populations, theory predicts that dispersal in fluctuating environments can facilitate asynchrony among clones and enhance stability by reducing temporal variability of total population abundance. This effect is predicted when clones exhibit heritable variation in environmental optima and when fluctuations occur asynchronously among patches. We tested this in the field using artificial ponds and metapopulations composed of a diverse assemblage of Daphnia pulex clones. We directly manipulated dispersal presence/absence and environmental fluctuations in the form of nutrient pulses. Consistent with predictions, dispersal enhanced temporal asynchrony among clones in the presence of nutrient pulses; this in turn stabilized population dynamics. This effect only emerged when patches experienced spatially asynchronous nutrient pulses (dispersal had no effect when patches were synchronously pulsed). Clonal asynchrony was driven by strong positive selection for a single clone that exhibited a performance advantage under conditions of low resource availability. Our work highlights the importance of dispersal as a driver of eco-evolutionary dynamics and population stability in variable environments.  相似文献   
99.
Leishmania species are dimorphic protozoan parasites that live and replicate in the gut of sand flies as promastigotes or in mammalian hosts as amastigotes. Different immune cells, including DCs, and receptors differ in their involvement in phagocytosis of promastigotes and amastigotes and in recognition of different Leishmania species. In the case of L. mexicana, differences in phagocytosis of promastigotes and amastigotes by DCs and participation of C‐type lectin receptors (CLRs) have not been established. In the present study, flow cytometry and confocal microscopy were used to investigate the phagocytosis by monocyte‐derived dendritic cells (moDCs) of L. mexicana promastigotes and amastigotes in the presence or absence of immune serum during various periods of time. Blocking antibodies against mannose receptors and DC‐SIGN were used to explore the participation of these receptors in the phagocytosis of L. mexicana by moDC. The major differences in interactions of L. mexicana promastigotes and amastigotes with moDC were found to occur within the first 3 hr, during which phagocytosis of promastigotes predominated as compared with opsonization of promastigotes and amastigotes. However, after 6 hr of incubation, opsonized promastigotes were preferentially phagocytosed as compared with unopsonized promastigotes and amastigotes and after 24 hr of incubation there were no differences in the phagocytosis of promastigotes and amastigotes. Finally, after 3 hr incubation, DC‐SIGN was involved in the phagocytosis of promastigotes, but not of amastigotes.  相似文献   
100.
The development of the intermediate lobe of the hypophysis was studied in the embryonic C3H mouse; at least four glands from embryos of every gestational day from 15 to 19 were examined. In the 16 day-old embryo prospective secretory cells proliferate at the centre of the intermediate lobe anlage. At the same stage cylindrical cells bordering the hypophyseal cleft begin to reorganize into marginal cells. By the end of fetal life marginal cells are well differentiated. In the 17 day-old embryo a few granular inclusions appear in some centrally located cells. Secretory cells increase in number during the following two embryonic days. Some of these cells contain polymorphic populations of granular and vesicular inclusions by gestational day 19. The possibility of a dual formation of secretory inclusions is discussed. The result implies that the onset of granule-formation by these cells is not contemporaneous with the start of production of melanophore-expanding substances, the presence of which has been detected by earlier biological assays.  相似文献   
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