In this study, we aimed to evaluate whether the encapsulation of ellagic acid (EA) into nanoliposomes would improve its potential in preventing cyclophosphamide-induced liver damage. Stability and ...antioxidative potential of free and encapsulated EA were determined. Experimental study conducted in vivo included ten groups of rats treated with cyclophosphamide and ellagic acid in its free and encapsulated form during 5 days. The protective effect of EA in its free and encapsulated form was determined based on serum liver function, liver tissue antioxidative capacities, and oxidative tissue damage parameters. Also, tissue morphological changes following cyclophosphamide administration were studied using standard histopathological and immunohistochemical analyses. The encapsulation of EA significantly prevented its degradation and improved its antioxidant properties in in vitro conditions. In in vivo experiments in both forms of EA were found to prevent rat liver damage induced by cyclophosphamide estimated through the changes in serum liver-damage parameters and tissue antioxidant capacities, as well as based on oxidatively modified lipids and proteins. Also, changes in morphology of liver cells and the expressions of Bcl-2, HIF-1α, and CD15 molecules in livers of animals of different experimental groups are in accordance with the obtained biochemical parameters. Thus, the encapsulation process might be effective in preventing EA from different environmental influences and could significantly increase its hepatoprotective potential. The encapsulation could prevent ellagic acid degradation and might deliver this potent compound to its target tissue in significantly larger quantities than when it is administered in its free form.
Febrile neutropenia is a serious chemotherapy-related adverse event that can lead to complications and death and it could be a significant burden on the organization of the health care system. The ...risk for febrile neutropenia is determined by chemotherapy-induced myelosuppression and the presence of patient-related risk factors. In the literature, various patient-related risk factors are taken into consideration. It was suggested that the patient age is the one of the most important ones. If the estimated risk for the febrile neutropenia is high, prophylactic use of myeloid growth factors (granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor) is recommended. In patients with solid tumors and lymphomas it was shown that the prophylactic use of myeloid growth factors significantly reduces the incidence of febrile neutropenia, early mortality during chemotherapy and infection-induced mortality. In patients who develop febrile neutropenia, there is less evidence for the therapeutic use of myeloid growth factors compared to prophylactic use, although there is a clear benefit in reducing the time to neutrophil count recovery. There is a clear benefit for hospitalized patients, also, in reducing duration of hospitalization. In patients with febrile neutropenia who have not been previously treated with prophylactic myeloid factors, assessment of risk factors for the complications is advised. In patients with high-risk febrile neutropenia therapeutic use of growth should be considered.
Introduction. Plurihormonal pituitary neuroendocrine tumours (PitNET)/adenomas are pituitary neuroendocrine tumours composed of monomorphous cell populations expressing anterior pituitary ...transcription factors and/or hormones belonging to more than one cell lineage. Studies dedicated to plurihormonal tumours are rare and quite heterogenous with their results, bearing in mind changes in diagnostic criteria and inconsistent use of antibodies for anterior pituitary transcription factors in the diagnostic immunohistochemical panel. Material and Methods. We retrospectively analysed all patients surgically treated for PitNETs from 2016 to July 2022 in a tertiary healthcare institution. All tumours previously diagnosed PitNETs with the word “plurihormonal” were re-examined and potentially re-classified, according to 2022 WHO classification of endocrine tumours. Results. Among 721 patients surgically treated for PitNET in 5.5 years period, the diagnosis of plurihormonal PitNET was established in 11 tumours (1.3%). All tumours showed diffuse and intensive positivity for anterior pituitary transcription factors PIT1 and SF1. Clinically, all patients presented with acromegaly. Conclusions. Retrospective studies related to newly defined plurihormonal PitNETs with a reassessment of diagnoses are necessary due to their rarity and ambition to investigate their origin and biological behaviour. The fact that the majority of plurihormonal PitNETs are clinically presented with acromegaly and show simultaneous positivity to PIT1 and SF1 transcription factors deserve special attention and need for further research in larger cohorts of these exceptional tumours.
Abstract Carbon dioxide sequestration from the atmosphere is commonly assessed using the eddy covariance method. Its net flux signal can be decomposed into gross primary production and ecosystem ...respiration components, but these have seldom been tested against independent methods. In addition, eddy covariance lacks the ability to partition carbon sequestration among individual trees or species within mixed forests. Therefore, we compared gross primary production from eddy covariance versus an independent method based on sap flow and water-use efficiency, as measured by the tissue heat balance method and δ13C of phloem contents, respectively. The latter measurements were conducted on individual trees throughout a growing season in a mixed broadleaf forest dominated by three tree species, namely English oak, narrow-leaved ash and common hornbeam (Quercus robur L., Fraxinus angustifolia Vahl, and Carpinus betulus L., respectively). In this context, we applied an alternative ecophysiological method aimed at verifying the accuracy of a state-of-the-art eddy covariance system while also offering a solution to the partitioning problem. We observed strong agreement in the ecosystem gross primary production estimates (R2 = 0.56; P < 0.0001), with correlation being especially high and nearly on the 1:1 line in the period before the end of July (R2 = 0.85; P < 0.0001). After this period, the estimates of gross primary production began to diverge. Possible reasons for the divergence are discussed, focusing especially on phenology and the limitation of the isotopic data. English oak showed the highest per-tree daily photosynthetic rates among tree species, but the smaller, more abundant common hornbeam contributed most to the stand-level summation, especially early in the spring. These findings provide a rigorous test of the methods and the species-level photosynthesis offers avenues for enhancing forest management aimed at carbon sequestration.
•Contrasting long-term growth trends in high vs. coppiced Quercus petraea trees are identified.•Past management drives sessile oak growth responses to climate warming.•Drought sensitivity in high ...forests is higher than in coppices.•The growth dynamic predicted for the 21st century is modulated by stand structure.•The legacy of management is leading the growth dynamics of coppice forests.
Climate extremes are expected to increase, which will affect oak forest ecosystems in Central European areas. Intensively managed forests, such as sessile oak stands, may alter their structure and function under a warming scenario. Here we analyse and project the climate-growth relationships of sessile oak (Quercus petraea) from high forests, originated from seed, and coppice forests, originated from vegetative reproduction in the Czech Republic. Dendrochronological data and linear mixed-effects models show similar effects of precipitation for April–May (positive) for both seedling- and coppice-origin trees. Previous autumn and current June temperature show significant negative correlations to growth in coppice forests. Nonetheless, trees from high forest stands showed increasing drought sensitivity and tended to show a stronger response to the previous autumn’s temperature during the 20th century. The positive effect of warmer autumns, only found on high stands, might be related to the extended growing season, suggesting improved adaptive capacity to cope with impending warmer conditions. In contrast, coppice trees might be able to buffer soil water shortage during spring and summer by higher root/shoot ratio. The obtained models were used to estimate the impact of 21st century-emission scenarios on tree basal area increments and stand basal area dynamics under different stand structures. Our results support that growth responses to climate warming are age and/or structure-dependent in sessile oak, particularly with regards to coppiced stands. Converting coppice forests to high stand structures, as well as thinning high stands, would enhance sessile oak forest adaptive capacity to cope with warming in Central Europe.
Stathmin1 is a microtubular regulatory protein. The expression disorders of this protein result in significant changes in cell migration, invasion, adhesion and colony formation in many malignant ...tumors. The aim of our research was to investigate the effects of Stathmin1 expression on neoangiogenesis in colorectal adenocarcinoma. Biopsy material that was obtained by the resection of colorectal carcinoma was used. The experimental group consisted of operative biopsies of colorectal cancer (n = 72), and the control group (n = 72) consisted of biopsies of adjacent non-tumor colon tissue. The biopsy material was taken from an operative preparation submitted to the Department of Pathology. After histopathological treatment, classical Hematoxylin- Eosin and immunohistochemical ABC methods with anti-Stathmin1, anti-VEGF and anti CD105 antibodies were applied on 4 µm thick sections. High expression of Stathmin1 is associated with severe (91.9%) and moderate (8.1%) expression of VEGF in a significantly high number of cases. This relation is defined by a highly significant correlation coefficient (r = 0.768; p = 0.000). High expression of Stathmin1 is associated with a high microvascular density index (mvdIDX) in a significant number of cases (73.0%) while low expression of Stathmin1 is in relation with low mvdIDX in a significant 73.7% of cases. This relationship is also defined by a highly significant correlation coefficient (r = 0.566; p = 0.000). ROC analysis showed that the sensitivity for Stathmin1 was 97.4% and the specificity was 91.4%. Based on Stathmin1 expression, it is possible to differentiate patients with increased risk for metastatic disease. The highly significant association of Stathmin1 expression with VEGF expression and microvascular density (MVD) suggests that Stathmin1 may be a serious candidate for therapeutic target.
Forest thinning can be used as an adaptive measure to improve the growth and resistance of Norway spruce forests affected by climate change. The impact of different thinning intensities on sap flow, ...growth, and tree water deficit of 40-year-old Norway spruce was tested. High thinning intensity (-61% of basal area) resulted in increased tree-level sap flow compared to the control (+27%), but it caused a decrease in the stand-level transpiration (-34%) due to reduced leaf area index. Low-intensity thinning (-28% basal area), high-intensity thinning, and control showed similar responses of sap flow to vapour pressure deficit and global radiation, suggesting unchanged isohydric behaviour. Both low- and high-intensity treatments displayed greater radial growth than the control. There were no differences in tree water deficit between the treatments. The low-intensity treatment can be considered the best water utilisation treatment with increased growth and unchanged transpiration at the tree level. The high-intensity treatment had similar radial growth as the low-intensity but lower stand-level transpiration, implying improved soil water availability. The study expands the ecophysiological understanding of thinning as a valuable silvicultural practice for adapting forest management of Norway spruce to the effects of climate change.
We have performed an in vitro study on isolated intact or denuded femoral artery (FA) of healthy, diabetic, and/or rats submitted to the FA occlusion. The aim was to determine the contribution of ...endothelium and endothelial dysfunction (ED) on serotonin-induced action in FA. Further, the contribution of angiotensin II and cyclooxygenase products of arachidonic acid was investigated. A marker of ED, vWF was measured in animal serum. Serotonin induced contraction-dependent contraction of isolated FA, which was increased in preparations with endothelium. Pathological conditions such as endothelial denudation, nicotine-induced ED, diabetes or occlusion of FA reduced serotonin-induced contraction. Comparable reduction of serotonin-induced contraction was achieved after inhibition of AT1 receptors with losartan in isolated FA with intact endothelium. Our results demonstrate that angiotensin II contributes to the enhancement of serotonin-induced contraction of femoral arteries with intact endothelium. This increase is attenuated by endothelium removal, nicotine treatment, vascular occlusion, and/or hyperglycemia.
Summary
Aims
The possible effect of vitamin D administration in humans on endothelial dysfunction (ED) still remains undetermined. The current meta‐analysis was performed to evaluate if vitamin D ...could improve ED.
Methods
Randomized, double‐blind, and placebo‐controlled clinical trials were identified by systematic search of the PubMed, the Cochrane Library, the Web of Science and the Scopus data bases, as well as different reviews and clinical trials articles. A random effects model was used to calculate the pooled overall effect on flow‐mediated dilation (FMD) linked to the vitamin D administration. Meta‐regression and subgroup analyses were performed to evaluate the impact of study characteristics on the effect of vitamin D administration on FMD.
Results
A total of eight studies with nine relevant study arms were identified. The obtained results of pooled analysis showed that vitamin D administration did not improve FMD (eight studies, 529 subjects; weighted mean difference (WMD): 0.96%, 95% CI: −1.24% to 2.06%; P = 0.09). This was probably due to significant heterogeneity in between included trials (I2 = 84%, P < 0.00001). On the other hand, subgroup analysis demonstrated that vitamin D improved FMD in trials that lasted <16 weeks; if systolic blood pressure (SBP) was higher than 140 mmHg and in trials where diastolic blood pressure (DBP) was <80 mmHg.
Conclusion
Although the current evidence clearly demonstrates that in certain conditions vitamin D can improve ED, a larger number of clinical trials are needed to confirm this assumption to confirm or reject the final statement on this topic.
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