The net effect of wealth on health-Investigating noncommunicable diseases mortality in the context of regional affluence.

The wealth-health relationship is not unambiguous and constant. Greater wealth affects individual and population health in opposite ways. Increased risk factors especially raise the probability of noncommunicable diseases (NCDs) impacting a population. Conversely, better healthcare and awareness reduce the chances of developing these diseases or increase the likelihood of treatment and cure. Therefore, this paper aims to assess and quantify the hard-to-grasp overall impact of prosperity on mortality from selected NCDs, allowing us to capture the relevant differences between European regions. In particular, we attempt to estimate the net effect of affluence and the health economic threshold of the GDP-mortality relationship, by developing a dedicated analytical tool based on joinpoint regression and forecasting methods. Our results show that in the case of most investigated diseases in more impoverished regions, a clear pattern reflects mortality rising with prosperity. After crossing the health economic threshold of around 20 thousand euros per capita, the trend changes by stabilising or reversing. The research we present shows that health policy should be more diversified locally to enable health convergence at the national and European regional levels. Moreover, health policy should evolve to prioritise mental and neurological disorders, by improving the resource allocation and increasing public awareness.

Polyphenolic-polysaccharide conjugates from medicinal plants of Rosaceae/Asteraceae family protect human lymphocytes but not myeloid leukemia K562 cells against radiation-induced death.

The aim of the study was to investigate whether the polyphenolic-polysaccharide conjugates (PPCs), isolated from flowers of Sanguisorba officinalis L. and Erigeron canadensis L., and from leaves of Fragaria vesca L. and Rubus plicatus Whe. Et N. E., can protect human peripheral blood mononuclear cells (PBMCs) against gamma-irradiation damage while maintaining the radiosensitivity of the myeloid leukemia K562 cell line. PPCs isolated from the four plant sources are water-soluble macromolecules (14-50 kDa) that were previously chemically and structurally characterized. Cells were incubated with PPCs (25 µg/ml, 1 h) prior exposure to 15 Gy gamma-irradiation, non-irradiated appropriate samples served as controls. It was found that the PPCs were able to increase the post-radiation viability of PBMCs by inhibiting apoptosis, while they did not protect the leukemic cells against radiation-induced apoptotic death. The PPCs offered an efficient protection of PBMCs through scavenging of intracellular ROS and decreasing DNA damage, while they provided no reduction of the oxidative stress and DNA damage in K562 cells. Our findings strongly suggest that the PPCs, especially these isolated from S. officinalis and E. canadensis, can selectively protect normal lymphocytes against radiation injury, therefore they meet the criteria of radioprotectors for potential use in radiotherapy.

Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients.

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2-D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients' blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α-2 macroglobulin, septin-14 and tubulin ß-1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet-origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro-coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.

Experimental reconstruction of an abdominal wall defect with electrospun polycaprolactone-ureidopyrimidinone mesh conserves compliance yet may have insufficient strength.

PURPOSE: Electrospun meshes mimic the extracellular matrix, which may improve their integration. We aimed to compare polycaprolactone (PCL) modified with ureidopyrimidinone (UPy) electrospun meshes with ultra-lightweight polypropylene (PP; Restorelle) reference textile meshes for in vivo compliance. We chose UPy-PCL because we have shown it does not compromise biomechanical properties of native tissue, and because it potentially can be bioactivated. METHODS: We performed ex vivo biomechanical cyclic loading in wet conditions and in vivo overlay of full-thickness abdominal wall defects in rats and rabbits. Animals were sacrificed at 7, 42 and 54 days (rats; n = 6/group) and 30 and 90 days (rabbits; n = 3/group). Outcomes were herniation, mesh degradation and mesh dimensions, explant compliance and histology. High failure rates prompted us to provide additional material strength by increasing fiber diameter and mesh thickness, which was further tested in rabbits as a biomechanically more challenging model. RESULTS: Compliance was tested in animals without herniation. In both species, UPy-PCL-explants were as compliant as native tissue. In rats, PP-explants were stiffer. Contraction was similar in UPy-PCL and PP-explants. However, UPy-PCL-meshes macroscopically degraded from 30 days onwards, coinciding with herniation in up to half of animals. Increased fiber and mesh thickness did not improve outcome. Degradation of UPy-PCL is associated with an abundance of foreign body giant cells until UPy-PCL disappears. CONCLUSION: Abdominal wall reconstruction with electrospun UPy-PCL meshes failed in 50%. Degradation coincided with a transient vigorous foreign body reaction. Non-failing UPy-PCL-explants were as compliant as native tissue. Despite that, the high failure rate forces us to explore electrospun meshes based on other polymers.

A comparative study on the radioprotective potential of the polyphenolic glycoconjugates from medicinal plants of Rosaceae and Asteraceae families versus their aglycones.

Radioprotective potential of the polyphenolic glycoconjugates, isolated from flowers of Sanguisorba officinalis L. (So) and Erigeron canadensis L. (Ec), and from leaves of Fragaria vesca L. (Fv) and Rubus plicatus Whe. Et N. E. (Rp) as well as their aglycones (SoA, EcA, FvA and RpA, respectively), against γ-radiation-induced lipid peroxidation in human plasma and DNA damage in lymphocytes, were investigated in vitro. These properties were assessed by measuring the concentration of thiobarbituric acid reactive substances (TBARS) and using the alkaline comet assay, and were compared to the protective effects of rutin (R) and quercetin (Q). Cytotoxicity of the glycoconjugates/aglycones towards L929 mouse fibroblasts and human lymphocytes were also measured. Plant products from S. officinalis, similar to Q, were able to reduce the most radiation-induced lipid peroxidation as well as DNA damage and extent of oxidative damage to the DNA basis. Contrary to the pure flavonoids, where Q was shown to be significantly more effective than its glycoside R, the results did not show more benefit with application of SoA/EcA over So/Ec in terms of lipid peroxidation inhibition. Moreover, glycoconjugates Ec and So showed much higher capacity in protecting lymphocytes against radiation-induced genotoxicity which may suggest that between the polyphenolic and polysaccharide parts exist some synergistic effects. There were no significant differences between Fv versus FvA or Rp versus RpA in terms of the provided radioprotection. Summarizing, plant glycoconjugates isolated by the multi-step method offered sufficient radioprotection. In addition, they possess many advantages, compared to the synthetic polyphenolic compounds or the plant extracts, such as water-solubility and minor toxicity.

Polyphenolic glycoconjugates from medical plants of Rosaceae/Asteraceae family protect human lymphocytes against γ-radiation-induced damage.

Radioprotective effects of the water-soluble polyphenolic glycoconjugates, isolated from flowers of Sanguisorba officinalis L.(SO) and Erigeron canadensis L.(EC), and from leaves of Fragaria vesca L. (FV) and Rubus plicatus Whe. Et N. E. (RP), against γ-radiation-induced toxicity in human peripheral blood lymphocytes were investigated. Cell treatment with glycoconjugates (1, 5 and 25µg/mL) prior exposure to 10/15Gy radiation resulted in concentration-dependent reduction of DNA damage including oxidative DNA lesions (comet assay), substantial inhibition of lipid peroxidation (TBARS) and restoration of superoxide dismutase and S-glutathione transferase activities. Glycoconjugates isolated from SO and EC ensured better protection versus these from RP and FV, with the SO product potential comparable to that of the reference quercetin. Strong antioxidant/radioprotective activity of the SO and EC glycoconjugates could be attributed to high abundance of syringol-type and ferulic acid units in their matrices, respectively. Moreover, polyphenolic glycoconjugates (25µg/mL), including RP and FV products, significantly decreased DNA damage when applied post-radiation suggesting their modulating effects on DNA repair pathways. Preliminary data on the glycoconjugate phenolic structural units, based on GLC/MS of the products of pyrolysis and in situ methylation, in relation to application of plant products as potential radioprotectors is promising and deserves further investigation.

Epigenetic changes in cancer by Raman imaging, fluorescence imaging, AFM and scanning near-field optical microscopy (SNOM). Acetylation in normal and human cancer breast cells MCF10A, MCF7 and MDA-MB-231.

This paper examines epigenetic changes in breast cancer by Raman imaging, fluorescence imaging, AFM and SNOM and discusses how they contribute to different aspects of tumourigenesis in malignant human breast epithelial cell lines MCF7 and MDA-MB-231 compared with non-malignant MCF10A cell lines. The paper focuses on information that can be extracted from Raman microscopy and Raman imaging for the biological material of nucleoli contained within the cell nucleus and lipid droplets within the cell cytoplasm. The biochemical composition of the nuclei and lipid droplets in the non-malignant and malignant human breast epithelial cell lines has been monitored. The potential of Raman microspectroscopy to monitor acetylation processes and a prognostic value of Raman biomarkers in breast cancer have been discussed.

Polyphenolic-polysaccharide conjugates from plants of Rosaceae/Asteraceae family as potential radioprotectors.

Polyphenolic-polysaccharide macromolecular, water-soluble glycoconjugates, isolated from the selected medicinal plants of Rosaceae/Asteraceae family: from leaves of Fragaria vesca L., Rubus plicatus Whe. et N. E., and from flowering parts of Sanguisorba officinalis L., and Erigeron canadensis L., were investigated for their ability to protect proteins and lipids of human plasma against γ-radiation-induced oxidative damage. Treatment of plasma with plant conjugates (6, 30, 150 µg/ml) prior exposure to 100 Gy radiation resulted in a significant inhibition of lipid peroxidation, evaluated by TBARS levels; conjugates isolated from E. canadensis and R. plicatus and a reference flavonoid quercetin showed similar high potential (approx. 70% inhibition, at 6 µg/ml). The conjugates prevented radiation-induced oxidation of protein thiols and significantly improved plasma total antioxidant capacity, estimated with Ellman's reagent and ABTS(.+) assay, respectively. The results demonstrate by the first time a significant radioprotective capability of the polyphenolic-polysaccharide conjugates isolated from E. canadensis, R. plicatus, S. officinalis and to the less extent from F. vesca. The abilities of these substances to inhibit radiation-induced lipid peroxidation and thiol oxidation in plasma seems to be mediated, but not limited to ROS scavenging activity.

The role of lipid droplets and adipocytes in cancer. Raman imaging of cell cultures: MCF10A, MCF7, and MDA-MB-231 compared to adipocytes in cancerous human breast tissue.

We have studied live non-malignant (MCF10A), mildly malignant (MCF7) and malignant (MDA-MB-231) breast cancer cells and human breast cancer tissue. We demonstrate the first application of Raman imaging and spectroscopy in diagnosing the role of lipid droplets in cell line cultures that closely mimic an in vivo environment of various stages in human breast cancer tissue. We have analyzed the composition of the lipid droplets in non-malignant and malignant human breast epithelial cell lines and discussed the potential of lipid droplets as a prognostic marker in breast cancer. To identify any difference in the lipid droplet-associated biochemistry and to correlate it with different stages of breast cancer, the PCA method was employed. The chemical composition of lipids and proteins, both in the cell line models and in human breast tissue has been analyzed. The paper shows the alterations in lipid metabolism that have been reported in cancer, at both the cellular and tissue levels, and discusses how they contribute to the different aspects of tumourigenesis.

Does quercetin protect human red blood cell membranes against γ-irradiation?

OBJECTIVES: Radioprotective potential of quercetin, a powerful free radical scavenger, was investigated in human red blood cells (RBCs) and in isolated RBC membranes exposed to γ-irradiation-induced oxidative stress. METHODS: RBCs and RBC membrane suspensions were irradiated (50 Gy) in the presence of quercetin (2-50 µM). Oxidative damage of the membranes was analysed by protein carbonyl measurement (enzyme-linked immunosorbent assay). In RBCs, the concentration of glutathione (GSH) was determined. Lipid peroxidation in RBCs, and for comparison in plasma and peripheral lymphocytes, was quantified by the amount of thiobarbituric acid-reactive substances (TBARS). Radiation-induced damage of the RBC membrane integrity was evaluated by the degree of haemolysis. RESULTS: Quercetin (50 µM) brought back the level of carbonyls to normal in γ-irradiated RBC membrane proteins and inhibited radiation-induced lipid peroxidation in plasma and lymphocytes, by 75 and 96%, respectively. However, it moderately decreased reduced/oxidized glutathione (GSH/GSSG) ratio and significantly increased TBARS concentrations, by 60 and 28% in irradiated and non-irradiated RBCs, respectively. Haemolysis rate was much higher in RBCs irradiated in the presence of quercetin vs. non antioxidant. DISCUSSION: In non-cellular systems (RBC membranes or plasma) and in lymphocytes, quercetin shows antioxidative/radioprotective activity but in whole RBCs it acts as a pro-oxidant and a cytotoxic substance. The possible mechanisms of such action are discussed.

[Cytokines modulate biology of tissue mast cells]. / Cytokiny moduluja biologie mastocytów tkankowych.

It is well documented that most if not all aspects of mast cell development, including growth, proliferation, and the differentiation/maturation are regulated by cytokines. Nowadays there is growing evidence that cytokines also influence the biology and function of mature tissue mast cells. Some cytokines activate mast cells directly to mediator release or modulate their reactivity to other stimulating agents. Various cytokines affect mast cells migration and expression of cell receptors, at the same time regulating the survival of tissue mast cells. Taking into account that mast cells themselves are the source of many cytokines (both preformed and newly generated) it can be assumed that these cytokines regulate the function of mast cells in tissues in autocrine manner.