Naringenin complexes with copper ions: potentiometric studies.

Flavanones belong to the group of active flavonoid compounds, rarely occurring in the plant kingdom and are found in many foodstuffs (naringenin and derivatives) and medicinal plant materials. Many studies have demonstrated a relationship between dietary intake of phenolic compounds and reduced risk of cancer and cardiovascular disease. Accordingly, during over several years, flavonoids have gained increasing interest and numerous studies have shown that they possess beneficial properties having a great influence on human health. Acid dissociation constants are believed to be the most useful physico-chemical parameters which describe the extent of ionization of functional groups as a function of pH. It is very important in research areas such as pharmaceutical drug discovery and development due to vital role in understanding the pharmacodynamic properties of new drug substances. Flavonoids are characterized by insolubility in water while they are soluble in organic solvents. Exploiting mixed solvents, especially organic solvent – water mixtures, enables a good alternative for researching on compounds which are inconspicuously soluble or insoluble in water. In this study the dissociation constant of naringenin and its complex with Cu(II) have been determined in aqueous – DMSO solvent mixtures to examine the dependence of their acid-base equilibria on number of substrates

Natural flavonoids: classification, potential role, and application of flavonoid analogues

Nowadays, it is assumed that natural flavonoids occurring in fruits and plant derived-foods are relevant, not only for organoleptic properties or technological reasons, but also because of their potential health-promoting effects, as suggested by the available experimental and epidemiological studies. This large group of phenolic plant constituents can be divided into several classes: flavanols, flavanones, flavonols, isoflavones, flavones and anthocyanins depending on the differences in their structures.The beneficial biological effects are also attributed to flavonoid analogues and their metal complexes. These compounds are characterized by antioxidant, pharmacological, anti-inflammatory, anti-allergic, antiviral, anticarcinogenic, as well as therapeutic and cytotoxic properties. Furthermore, they possess a wide range of applications including various fields of industry. DOI: http://dx.doi.org/10.5281/zenodo.54577

Antioxidant activity of extracts from defatted and non-defatted flax (Linum usitatissimum L.) seeds

Flax, Linum usitatissimum, is an annual plant and member of the Linaceae family [1]. Flax is rich in fats (41%), proteins (20%) and dietary fibre (28%). Seeds of flax are the richest source of alpha-linolenic acid, lignans and other nutritional components. Flaxseed oil contains interesting bioactive compounds other than the fats [2]. The aim of this study was to estimate the total polyphenol content (TPC), free radical scavenging activity, and ferric reducing antioxidant power (FRAP) in extracts from defatted and non-defatted flax seeds. The results clearly show the impact of fatty acids on the effectiveness of this research

Determination of total contents of transition metals in selected granular black teas marketed in Poland

The total contents of metals in three granulated black tea samples marketed in Poland were determined. Four elements consisting transition metals (Ni, Cu, Zn and Fe) were analyzed using flame atomic absorption spectrophotometry (FAAS). All examined tea brands contain considerable contents of the studied transition metals. Among the tested transition metals Fe (242-589 mg kg-1) was the most abundant one in the granular black tea imported from India. The highest value of Fe was analyzed in the cheapest tea, the smallest in the most expensive. The other metals are less abundant than Fe, their values varied from 8.50-8.90 for Ni, 7.80-10.4 for Cu and 8.13-12.6 for Zn mg kg-1. The accuracy of the proposed method was assessed by determining the recovery of metals from analyzed tea samples using the standard addition method. Recovery assays of nickel, copper, zinc and iron were demonstrated satisfactory, mean recoveries 99.29, 100.31, 99.94 and 99.79 %, respectively

Naringenin Schiff base: antioxidant activity, acid–base profile, and interactions with DNA

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Aminoimidazole Carboxamide Ribonucleotide (AICAR) Inhibits the Growth of Retinoblastoma In Vivo by Decreasing Angiogenesis and Inducing Apoptosis

5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma

Determining the enzymatic activities of iodothyronine 5’-deiodinases in renal medulla and cortex

Wstęp: Zaburzenia hormonów tarczycy u pacjentów z przewlekłą chorobą nerek (PChN) są wynikiem zaburzeń konwersji T4 do T3. Znaczenie nerek w konwersji hormonów tarczycy nie jest w pełni poznane. Działania różnych typów dejodynaz jodotyroninowych w strukturach nerek, nie zostały jeszcze określone. Celem badań było określenie aktywności dejodynazy typu 1 (D1) i typu 2 (D2) w korze i rdzeniu nerek u chorych z rakiem nerki. Materiał i metody: Próbki kory i rdzenia nerek (10 pacjentów) lub tylko samej kory (13 pacjentów) były pobrane z przeciwnego bieguna tej samej nerki do guza , z nerek usuniętych z powodu raka. Resekcje wykonano u 23 chorych (7 kobiet i 16 mężczyzn) w wieku 52&#8211;82 lat. Wyniki: Aktywność D1 w korze nerki wynosiła 3,785 &#177; 2,041 fmol 125I/mg białka/min., a aktywność D2 wynosiła 0,236 &#177; 0,125 fmol 125I/ mg białka/min. Znaleziono silną, dodatnią korelację pomiędzy aktywnością D1 i D2 w korze nerki (r = 0,890, p < 0,001). Aktywność D1 w rdzeniu nerek wynosiła 2,157 &#177; 2,176 fmol 125I/mg białka /min., a aktywność D2 wynosiła 0,168 &#177; 0,095 fmol 125I/mg białka/min. Zaobserwowano również dodatni związek pomiędzy aktywnością D1 i D2 w rdzeniu nerek (r = 0,661, p = 0,038). Stwierdzono silną dodatnią korelację aktywności D1 w korze i rdzeniu (r = 0,794, p = 0,006) oraz brak korelacji aktywności D2 w korze i rdzeniu (r = 0,224, p = 0,553). Wnioski: Wyniki przedstawionej pracy sugerują, że aktwność dejodynaz 1 i 2 zarówno w korze jak i w rdzeniu nerki może miec wpływ na metabolizm hormonów tarczycy. To ustalenie może mieć znaczenie kliniczne dla chorych z upośledzoną funkcją nerek. (Endokrynol Pol 2013; 64 (3): 182&#8211;185)Introduction: Thyroid hormone disorders in patients with chronic kidney disease (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys in thyroid hormones conversion is not fully understood. The activities of different types of iodothyronine deiodinases in the kidney structures have not been determined yet. The aim of this study was to determine the activity of deiodinase type 1 (D1) and type 2 (D2) in renal cortex and medulla in renal cancer patients. Material and methods: Samples of renal cortex and medulla (ten patients) or renal cortex alone (13 patients) were taken from kidneys resected because of malignant cancer, from a site opposite to the cancer. Resections were performed in the 23 patients (seven female and 16 male) who were 52&#8211;82 years old. The material was stored at &#8211;72 oC. Results: Activity of D1 in renal cortex was 3.785 &#177; 2.041 fmol 125I/mg protein/minute and activity of D2 was 0.236 &#177; 0.125 fmol 125I/mg protein/minute. There was a strong positive correlation between D1 and D2 activities in renal cortex (r = 0.890, p < 0.001). Activity of D1 in renal medulla was 2.157 &#177; 2.176 fmol 125I/mg protein/minute, and activity of D2 was 0.168 &#177; 0.095 fmol 125I/mg protein/minute. A positive correlation between D1 and D2 in renal medulla (r = 0.661, p = 0.038) was observed as well. Activities of D1 in cortex and medulla were strongly and positively associated (r = 0.794, p = 0.006), whereas there was no correlation between the activities of D2 in cortex and medulla (r = 0.224, p = 0.553). Conclusions: Results presented in this study suggest that both cortical and medullary D1 and D2 may be involved in thyroid hormone metabolism. This finding could be of clinical relevance in patients with impaired renal function. (Endokrynol Pol 2013; 64 (3): 182&#8211;185

EGF-Like-Domain-7 Is Required for VEGF-Induced Akt/ERK Activation and Vascular Tube Formation in an Ex Vivo Angiogenesis Assay

EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization

EGF-Like-Domain-7 Is Required for VEGF-Induced Akt/ERK Activation and Vascular Tube Formation in an Ex Vivo Angiogenesis Assay

EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization

Effects of metformin on retinoblastoma growth in vitro and in vivo

Recent studies suggest that the anti-diabetic drug metformin may reduce the risk of cancer and have anti-proliferative effects for some but not all cancers. In this study, we examined the effects of metformin on human retinoblastoma cell proliferation in vitro and in vivo. Two different human retinoblastoma cell lines (Y79, WERI) were treated with metformin in vitro and xenografts of Y79 cells were established in nu/nu immune-deficient mice and used to assess the effects of pharmacological levels of metformin in vivo. Metformin inhibited proliferation of the retinoblastoma cells in vitro. Similar to other studies, high concentrations of metformin (mM) blocked the cell cycle in G0–G1, indicated by a strong decrease of G1 cyclins, especially cyclin D, cyclin-dependent kinases (4 and 6), and flow cytometry assessment of the cell cycle. This was associated with activation of AMPK, inhibition of the mTOR pathways and autophagy marker LC3B. However, metformin failed to suppress growth of xenografted tumors of Y79 human retinoblastoma cells in nu/nu mice, even when treated with a maximally tolerated dose level achieved in human patients. In conclusion, suprapharmacological levels (mM) of metformin, well above those tolerated in vivo, inhibited the proliferation of retinoblastoma cells in vitro. However, physiological levels of metformin, such as seen in the clinical setting, did not affect the growth of retinoblastoma cells in vitro or in vivo. This suggests that the potential beneficial effects of metformin seen in epidemiological studies may be limited to specific tumor types or be related to indirect effects/mechanisms not observed under acute laboratory conditions