Plasma selenium levels in rheumatoid arthritis

The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p<0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p<0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p>0.05). Our results suggest that Se is an important factor in RA.     

Cytotoxic activity of 4'-hydroxychalcone derivatives against Jurkat cells and their effects on mammalian DNA topoisomerase I

Chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Several reports have shown that compounds with cytotoxic properties may also interfere with DNA topoisomerase functions. Five derivatives of 4'-hydroxychalcones were examined for cytotoxicity against transformed human T (Jurkat) cells as well as plasmid supercoil relaxation experiments using mammalian DNA topoisomerase I. The compounds were 3-phenyl-1-(4'-hydroxyphenyl)-2-propen-1-one (I), 3-(p-methylphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one (II), 3-(p-methoxyphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one (III), 3-(p-chlorophenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one (IV), and 3-(2- thienyl)-1-(4'-hydroxyphenyl)-2-propen-1-one (V). The order of the cytotoxicity of the compounds was; IV > III > II > I > V. Compound IV, had the highest Hammett and log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity and strongest DNA topoisomerase I inhibition. Compounds I and II gave moderate interference with the DNA topoisomerase I while III & V did not interfere with the enzyme.     

Gossypol Interferes with Both Type I and Type II Topoisomerase Activities Without Generating Strand Breaks

A considerable number of agents with chemotherapeutic potentials reported over the past years were shown to interfere with the reactions of DNA topoisomerases, the essential enzymes that regulate conformational changes in DNA topology. Gossypol, a naturally occurring bioactive phytochemical is a chemopreventive agent against various types of cancer cell growth with a reported activity on mammalian topoisomerase II. The compounds targeting topoisomerases vary in their mode of action; class I compounds act by stabilizing covalent topoisomerase-DNA complexes resulting in DNA strand breaks while class II compounds interfere with the catalytic function of topoisomerases without generating strand breaks. In this study, we report Gossypol as the interfering agent with type I topoisomerases as well. We also carried out an extensive set of assays to analyze the type of interference manifested by Gossypol on DNA topoisomerases. Our results strongly suggest that Gossypol is a potential class II inhibitor as it blocked DNA topoisomerase reactions with no consequently formed strand breaks.     

Suppressive Role of Boron on Adipogenic Differentiation and Fat Deposition in Human Mesenchymal Stem Cells

Biological Trace Element Research - Over the past years, adipose tissue has become an invaluable source of mesenchymal stem cells (MSCs) due to development of improved isolation methodologies. In a...     

Investigation of acetylcholinesterase and mammalian DNA topoisomerases,carbonic anhydrase inhibition profiles,and cytotoxic activity of novel bis(α‐aminoalkyl)phosphinic acid derivatives against human breast cancer

The aim of this study was to evaluate biologically active novel molecules having potentials to be drugs by their antitumor properties and by activities of apoptotic caspase and topoisomerase. Following syntheses of novel eight bis(α‐aminoalkyl)phosphinic acid derivatives ( 4a–h ) as a result of array of reactions, compounds were evaluated by cytotoxic effects in vitro on human breast cancer (MCF‐7) and normal endothelial (HUVEC) cell lines. All phosphinic acid derivatives were effective for cytotoxicity on both MCF‐7 and HUVEC lines, while 4c , 4e , and 4f compounds were found significantly more effective. For the evaluation of antitumor properties of compounds in a highly sensitive method, their effects on inhibiting topoisomerases I and II were investigated. Also, some of the bis(α‐aminoalkyl)phosphinic acid derivatives ( 4a, 4e–h ) showed nice inhibitory action against acetylcholinesterase and human carbonic anhydrase isoforms I and II.     

The distribution of the bft alleles among enterotoxigenic Bacteroides fragilis strains from stool specimens and extraintestinal sites

Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in diarrhoeal illness in animals and humans. Recent data suggest that ETBF is associated with flares of inflammatory bowel disease. Toxigenicity is attributed to expression of a toxin referred to as fragilysin, which stimulates fluid accumulation in ligated intestinal segments and alter the morphology of human intestinal cells. Three different isoforms or variants of the enterotoxin gene, designated bft-1, bft-2, and bft-3, have been identified. In this study we investigated the distribution of bft alleles among ETBF strains in stool specimens from patients with colon cancer (n: 31), the control patients (n: 8) and extraintestinal sources (n: 15). We used restriction fragment length polymorphism analysis of the PCR-amplified enterotoxin gene and sequencing the PCR-product to detect the isoforms of bft gene. Among the stool strains, bft-1 was found to be more common than bft-2; as it was detected 27 of 31 strains from colon cancer patients and 7 of 8 control strains. The bft-1 isoform was also found in almost all isolates from extraintestinal sites. No bft-3 subtype was detected among all tested strains.     

Biological activity of 1-aryl-3-phenethylamino-1-propanone hydrochlorides and 3-aroyl-4-aryl-1-phenethyl-4-piperidinols on PC-3 cells and DNA topoisomerase I enzyme

A number of studies reported Mannich bases to manifest antimicrobial, cytotoxic, anticancer, anti-inflammatory, and anticonvulsant activities. A considerable number of therapeutically important cytotoxic compounds are active on DNA topoisomerases that regulate the DNA topology. In the present study we evaluated the biological activity of mono-Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides (1a-10a), and semicyclic mono-Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols (1b-9b), synthesized in our laboratory. We employed androgen-independent human prostate cancer cells (PC-3) to assess the cytotoxicity of the compounds and extended the biological activity evaluation to cover supercoil relaxation assays of mammalian type I topoisomerases. Our results showed that the compounds had cytotoxicity within the 8.2-32.1 microM range, while two compounds gave rise to a comparable average value in topo I interference of 42% and 40% for 10a (with a hydroxy substituent on the phenyl ring from mono-Mannich bases) and 5b (with a fluoro substituent on the phenyl ring from the semicyclic mono-Mannich base series, piperidinols), respectively.     

Plasma and erythrocyte lipid peroxide levels in workers with occupational exposure to lead

The plasma and erythrocyte lipid peroxide levels were measured in a group of male subjects occupationally exposed to lead for an average period of 17 yr, and compared to those from an age-matched control group living in the same city in a similar socioeconomical environment. The blood lead and plasma zinc levels were measured by atomic absorption spectroscopy. The plasma and erythrocyte lipid peroxide levels were established by the malondialdehyde determination method. Significant differences were found in the blood lead levels in lead-exposed workers, 15.00±10.15 μg/dL as compared to controls, 2.37±0.89 μg/dL. The plasma (2.67±0.69 μM) and erythrocyte (27.53±6.28 nmol/g Hb) lipid peroxide levels in workers with occupational exposure to lead were significantly higher than controls, 1.23±0.61 μM and 14.35±2.08 nmol/g Hb, respectively. There were no significant differences of the zinc levels in both groups. The blood lead levels had a statistically significant positive correlation with age and with duration of exposure in both groups, but showed no relationship to the corresponding blood zinc levels. The results presented in this study indicate that the increase of plasma and erythrocyte lipid peroxide levels in workers exposed to lead may be related to the lead concentration, age and duration of exposure.     

Cytotoxic activity of 4′-hydroxychalcone derivatives against Jurkat cells and their effects on mammalian DNA topoisomerase I

Chalcones (1,3-diaryl-2-propen-1-ones) are α, β-unsaturated ketones with cytotoxic and anticancer properties. Several reports have shown that compounds with cytotoxic properties may also interfere with DNA topoisomerase functions. Five derivatives of 4′-hydroxychalcones were examined for cytotoxicity against transformed human T (Jurkat) cells as well as plasmid supercoil relaxation experiments using mammalian DNA topoisomerase I. The compounds were 3-phenyl-1-(4′-hydroxyphenyl)-2-propen-1-one (I), 3-(p-methylphenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (II), 3-(p-methoxyphenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (III), 3-(p-chlorophenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (IV), and 3-(2- thienyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (V). The order of the cytotoxicity of the compounds was; IV > III > II > I > V. Compound IV, had the highest Hammett and log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity and strongest DNA topoisomerase I inhibition. Compounds I and II gave moderate interference with the DNA topoisomerase I while III & V did not interfere with the enzyme.