Quantitative Analysis of Serum Zinc Levels in Primary Brain Tumor Patients.

Although the close relationships between most of the trace elements and tumor formation mechanisms are very well-defined, studies on some elements such as zinc are still ongoing. When examining studies on brain tumors, it was observed that studies investigating the role played by serum zinc levels on tumor etiology and prognosis have gained momentum. In this study, we investigate the relationship between different brain tumor types and serum zinc levels by quantitatively analyzing serum zinc levels in patients with primary brain tumors. In this study, we measured serum zinc levels of 33 brain tumor patients as well as 35 healthy individuals serving as a control group. Metal concentrations were measured using atomic absorption spectrophotometry. Serum zinc levels were lower in patients with primary brain tumors compared to control group (p < 0.05). Additionally, patients' serum zinc levels were significantly different according to their brain tumor types and also according to their age (p < 0.05). Our findings suggest that brain tumor patients' serum zinc levels may play a role in tumor etiology, typology, and prognosis.

Borax Pentahydrate and Disodium Pentaborate Decahydrate Are Candidates as Anti-leukemic Drug Components by Inducing Apoptosis and Changing Bax/Bcl-2 Ratio in HL-60 Cell Line.

Acute myeloid leukemia (AML) is the most common form of acute leukemia and has the lowest 5-year survival rates. Current treatment strategies do not meet the expectations also. Therefore, there is a need to improve therapeutic approaches still. Boron, which is a natural trace element in human diet, is gaining attention with its important roles in cellular processes for the development of new anti-cancer drug candidates. For instance, bortezomib, a dipeptidyl boronic acid, has encouraging results in the treatment of multiple myeloma and mantle cell lymphoma. However, severe toxic effects and resistance development are the limitations to its application for AML treatment. Hence, the development of alternative boron-derived anti-AML agents is unmet need. Therefore, we aimed to evaluate anti-leukemic effect of two promising boron compounds, borax pentahydrate (BP) and disodium pentaborate decahydrate (DPD), and comparison of each other in terms of the capacity to trigger apoptosis on acute promyelocytic leukemia cells (HL-60). Cell viability was assessed by MTT assay. Apoptotic effects of the boron compounds on HL-60 cells were evaluated by annexin V/propidium iodide dyes and caspase 3/7 activity assay by flow cytometry. In addition, Bax/Bcl-2 and cleaved PARP levels were detected by western blotting. Although BP showed greater apoptosis-inducing capacity, we observed that both DPD (6 mM) and BP (24 mM) treatment showed anti-leukemic effect by triggering apoptotic pathway through increasing Bax/Bcl-2 ratio for the first time. Our study suggests that BP and DPD are the promising candidates for anti-AML drug development research, which may be confirmed by further wide-spectrum studies.

Combinations of polyphenols disaggregate Aß1­42 by passing through in vitro blood brain barrier developed by endothelium, astrocyte, and differentiated SH­SY5Y cells.

Disaggregation of amyloid ßeta (Aß) is considered as one of the promising therapeutic strategies for Alzheimer's disease. Polyphenols are promising molecules for the disaggregation of Aß. However, in order to find a potential therapeutic candidate, the in vitro analyses need to be performed on a model that mimics the blood­brain barrier (BBB) as much as possible. Therefore, we aimed to establish an in vitro BBB representative transwell system by using differentiated human neuroblastoma (SH­SY5Y), cerebral microvascular endothelial, and astrocyte cells to investigate transition and Aß disaggregation capacity of punicalagin (PU), ellagic acid (EA), epigallocatechin gallate (EGCG), gastrodin, and their combinations on the established system. The efficiency of the established transwell systems was evaluated by measuring the transendothelial electrical resistance (TEER) and paracellular permeability coefficients (Pe) values. The transition and Aß disaggregation capacities of the polyphenols were evaluated in the established tri­culture transwell system based on obtained TEER (50,07 Ω.cm2) and Pe (65x10­6 cm/s) values. Our results revealed that all polyphenols can successfully pass across the BBB system and disaggregate Aß. While Aß disaggregation capacities of the polyphenols were in the range of 30.52-45.01%, the percentages of their combinations were higher (75% for EGCG­PU (Com 1) and 64% for EGCG­EA (Com 2)). Consequently, this study provides the first evidence that Com 1 and Com 2 are promising polyphenol combinations in terms of Aß disaggregation. Besides, the developed tri­culture transwell system, containing differentiated SH­SY5Y cells, may provide a new tool that closely mimics the BBB for basic research and testing of candidate agents.

Melatonin attenuates the detrimental effects of UVA irradiation in human dermal fibroblasts by suppressing oxidative damage and MAPK/AP-1 signal pathway in vitro.

BACKGROUND: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen-activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP-1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures. OBJECTIVES: In this study, we investigated the effects of melatonin on UVA-irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time-dependent manner which have not been clearly elucidated yet. METHODS: To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub-cytotoxic dosage (20 J/cm2 ) after pretreatment with melatonin (1 µmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points. RESULTS: Our results clearly show that melatonin decreases UVA-induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP-1 signal transduction pathway and production of matrix metalloproteinases in a time-dependent manner. CONCLUSION: Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation.