Soils selenium level and esophageal cancer: An ecological study in a high risk area for esophageal cancer

ProjectGolestan province, located in northeast of Iran, has been known as a high risk area for esophageal cancer (EC). This study was conducted to assess the relationship between soils selenium (Se) level and development of EC in this region.ProceduresIn this ecological study, 135 blocks were identified in Golestan province based on geographical altitude and longitude on the map. One soil sample was collected from the center of each block. Then we investigated Se concentration in soil samples by flame atomic absorption spectrometry. Statistical analysis was performed by the Pearson correlation test and Student t-tests. P-values of less than 0.05 were considered as significant.ResultsThe mean±SD of soils Se level in Golestan province was 3.7±1.61 mg/kg. There was a positive correlation between soils Se level and EC rates in this area (P=0.03) (Pearson correlation coefficient=0.19). Soils Se concentration was significantly higher in high (4.13 mg/kg) than in the low (3.39 mg/kg) EC rate areas (P=0.01).ConclusionsWe found high soils Se concentration and a significant positive relationship between soils Se level and EC rate in Golestan province of Iran. So, high soils Se level may play a possible role in developing EC in this area, specifically in Turkmensahra (very high EC rates).     

Modification of PAHs Biodegradation with Humic Compounds

The effect of extractable humic substances (EHS) on the bioremediation of phenanthrene in a slurry phase was investigated using adapted microorganisms with polycyclic aromatic hydrocarbons (PAHs). Two concentrations of EHS were used: 150 and 30 mg/kg soil. The phenanthrene concentration was 500 mg/kg soil. The results showed that the trend of biodegradation was increased after four weeks retardation. These tests showed that humic compounds could overcome the bond between the soil and phenanthrene in the presence of the bacterial consortium. The bacterial density in the medium with EHS was about six-fold greater in magnitude than in the medium without the humic compounds. The chemical relationship between phenanthrene and the humic substances in the form of a phenanthrene-humic-soil complex or phenanthrene-humic is loosely associated and reversible. Therefore, after the initial inhibition by humic substances, the bioavailability of phenanthrene increases.     

Hepatic over-expression of peroxisome proliferator activated receptor γ2 in the ob/ob mouse model of non‐insulin dependent diabetes mellitus

The binding of nuclear factor on the promoter region of the regucalcin gene and the expression of regucalcin in the kidney cortex of rats was investigated. Nuclear extracts from kidney cortex were used for oligonucleotide competition gel mobility shift assay. An oligonucleotide between position –523 and –506 in the 5-flanking region of the rat regucalcin gene, which contains a nuclear factor I (NF1) consensus motif TTGGC(N)₆CC, competed with the probe for the binding of the nuclear protein from kidney cortex. The mutation of TTGGC in the consensus sequence caused an inhibition of the binding of nuclear factors. The binding of nuclear factor on the 5-flanking region was clearly reduced in the kidney cortex obtained at 1, 2, and 3 days after a single intraperitoneal administration of cisplatin (1.0 mg/100 g body wt) to rats. Moreover, cisplatin administration caused a remarkable decrease in regucalcin mRNA levels and regucalcin concentration in the kidney cortex. Also, serum regucalcin concentration was significantly decreased by cisplatin administration. Meanwhile, serum urea nitrogen concentration was markedly elevated by cisplatin administration. The present study demonstrates that the specific nuclear factor binds to the NF1-like sequence in the promotor region of regucalcin gene in the kidney cortex of rats, and that the nuclear factor binding and regucalcin expression are suppressed by cisplatin administration.     

Brugia malayi microfilariae induce cell death in human dendritic cells,inhibit their ability to make IL-12 and IL-10, and reduce their capacity to activate CD4+ T cells

Parasite Ag-specific T cell unresponsiveness and diminished IFN-gamma production are immunologic hallmarks of patent infection with lymph-dwelling filarial nematodes. Although this diminished responsiveness is directed primarily against the intravascular microfilarial (MF) parasite stage and mediated in part by reduced APC function, the mechanisms involved are not fully understood. In this report, we demonstrate that human dendritic cells (DC) exposed to live MF up-regulate both the cell surface and gene expression of CD54 (ICAM-1). Moreover, live MF result in a 3-fold increase in DC death compared with MF-unexposed DC, primarily due to apoptosis. Notably, microarray and real-time RT-PCR data indicate that live MF concurrently up-regulate mRNA expression of proinflammatory molecules such as IL-8, RANTES, IL-1alpha, TNF-alpha, and IL-beta in DC, the presence of which is also detected at the protein level, while inhibiting the production of IL-12 (p40 and p70) and IL-10. Soluble excretory-secretory products from live MF diminished IL-12 and IL-10 production and induced DC death, although to a lesser degree. Moreover, exposure of DC to live MF resulted in a decrease in the ability of DC to promote CD4(+) T cell production of IFN-gamma and IL-5. Our findings clearly suggest that the interaction between live MF and DC is complex but contributes to the hyporesponsiveness and parasite persistence associated with the MF(+) state in the infected human. These data further suggest that MF induce an orchestrated response in APC that leads to a diminished capacity to function appropriately, which in turn has significant consequences for CD4(+) T cells.     

Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole‐Phenylpiperazine Derivatives

In this work, a novel series of arylisoxazole‐phenylpiperazines were designed, synthesized, and evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our results revealed that [5‐(2‐chlorophenyl)‐1,2‐oxazol‐3‐yl](4‐phenylpiperazin‐1‐yl)methanone ( 5c ) was the most potent AChE inhibitor with IC₅₀ of 21.85 μm . It should be noted that most of synthesized compounds showed no BChE inhibitory activity and [5‐(2‐fluorophenyl)‐1,2‐oxazol‐3‐yl](4‐phenylpiperazin‐1‐yl)methanone ( 5a ) was the most active anti‐BChE derivative (IC₅₀=51.66 μm ). Also, kinetic studies for the AChE and BChE inhibitory activity of compounds 5c and 5a confirmed that they have simultaneously bound to the catalytic site (CS) and peripheral anionic site (PAS) of both AChE and BChE. Furthermore, docking study of compound 5c showed desired interactions of that compound with amino acid residues located in the active and peripheral anionic sites. Compound 5c was also evaluated for its BACE1 inhibitory activity and demonstrated IC₅₀=76.78 μm . Finally, neuroprotectivity of compound 5c on Aβ‐treated neurotoxicity in PC12 cells depicted low activity.     

Rapid Adsorption of Copper(II) and Lead(II) by Rice Straw/Fe3O4 Nanocomposite: Optimization,Equilibrium Isotherms,and Adsorption Kinetics Study

Rice straw/magnetic nanocomposites (RS/Fe₃O₄-NCs) were prepared via co-precipitation method for removal of Pb(II) and Cu(II) from aqueous solutions. Response surface methodology (RSM) was utilized to find the optimum conditions for removal of ions. The effects of three independent variables including initial ion concentration, removal time, and adsorbent dosage were investigated on the maximum adsorption of Pb (II) and Cu (II). The optimum conditions for the adsorption of Pb(II) and Cu(II) were obtained (100 and 60 mg/L) of initial ion concentration, (41.96 and 59.35 s) of removal time and 0.13 g of adsorbent for both ions, respectively. The maximum removal efficiencies of Pb(II) and Cu(II) were obtained 96.25% and 75.54%, respectively. In the equilibrium isotherm study, the adsorption data fitted well with the Langmuir isotherm model. The adsorption kinetics was best depicted by the pseudo-second order model. Desorption experiments showed adsorbent can be reused successfully for three adsorption-desorption cycles.     

Evaluation of the yeast-extract signaling pathway leading to silymarin biosynthesis in milk thistle hairy root culture

The biosynthesis of silymarin, a potent antihepatotoxic compound, from the dried fruits of Silybum marianum L. Gaertn in hairy root cultures can be stimulated by a yeast extract elicitor. These results correlated with culture time, and the biosynthesis reached a maximum of 0.47 mg g^?1 DW by 72 h after culture (2-fold higher than the control). Lipoxygenase activity and linoleic acid content were stimulated by this treatment, suggesting that the jasmonate pathway may mediate the elicitor-induced accumulation of silymarin. The H₂O₂ content increased 24 h after elicitation and did not have marked changes between 48 and 72 h. In addition, the tocopherol content (especially α- and δ-tocopherols) increased 72 h after elicitation in comparison with non-treated cultures. Ascorbate had trace changes during feeding time and was lower than the control. The antioxidant activity was assayed by the 1-1-diphenyl-2-picrylhydrazyl stable free radical method and results were calculated base on an IC₅₀ that increased upon treatment, especially 24 h after treatment, with changes related to H₂O₂ content. These observations suggested that reactive oxygen species may mediate elicitor signals to the jasmonate pathway that lead to the production of silymarin.     

Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using two‐dimensional polyacrylamide gel electrophoresis and mass spectrometry

Obstructive sleep apnea (OSA) affects an estimated 20% of adults worldwide and has been associated with electrical and structural abnormalities of the atria, although the molecular mechanisms are not well understood. Here, we used two‐dimensional polyacrylamide gel electrophoresis (2D PAGE) coupled with nanoliquid chromatography‐tandem mass spectrometry (nanoLC‐MS/MS) to investigate the proteins that are dysregulated in the atria from severe and moderate apnea when compared to control. We found enzymes involved in the glycolysis, beta‐oxidation, electron transport chain and Krebs cycle to be down‐regulated. The data suggested that the dysregulated proteins may play a role in atrial pathology developing via chronic obstructive apnea and hypoxia. Our results are consistent with our previous 1D‐PAGE and nanoLC‐MS/MS study (Channaveerappa et al, J Cell Mol Med. 2017), where we found that some aerobic and anaerobic glycolytic and Krebs cycle enzymes were down‐regulated, suggesting that apnea may be a result of paucity of oxygen and production of ATP and reducing equivalents (NADH). The 2D‐PAGE study not only complements our current study, but also advances our understanding of the OSA. The complete mass spectrometry data are available via ProteomeXchange with identifier PXD011181.     

The acute-phase protein serum amyloid A induces endothelial dysfunction that is inhibited by high-density lipoprotein

The acute-phase protein serum amyloid A (SAA) is elevated during inflammation and may be deposited in atheroma where it promotes atherosclerosis. We investigated the proatherogenic effects of SAA on the vascular endothelium and their regulation by high-density lipoprotein (HDL). Exposure of human aortic endothelial cells (HAEC) to SAA (0.25-25 μg/ml) decreased nitric oxide (^•NO) synthesis/bioavailability, although the endothelial NO synthase monomer-to-dimer ratio was unaffected. SAA (10 μg/ml) stimulated a Ca²⁺ influx linked to apocynin-sensitive superoxide radical anion (O₂^•−) production. Gene expression for arginase-1, nuclear factor κB (NF-κB), interleukin-8, and tissue factor (TF) increased within 4 h of SAA stimulation. Enzymatically active Arg-1/2 was detected in HAEC cultured with SAA for 24 h. Therefore, in addition to modulating ^•NO bioavailability by stimulating O₂^•− production in the endothelium, SAA modulated vascular l-Arg bioavailability. SAA also diminished relaxation of preconstricted aortic rings induced by acetylcholine, and added superoxide dismutase restored the vascular response. Preincubation of HAEC with HDL (100 or 200, but not 50, μg/ml) before (not after) SAA treatment ameliorated the Ca²⁺ influx and O₂^•− production; decreased TF, NF-κB, and Arg-1 gene expression; and preserved overall vascular function. Thus, SAA may promote endothelial dysfunction by modulating ^•NO and l-Arg bioavailability, and HDL pretreatment may be protective. The relative HDL to SAA concentrations may regulate the proatherogenic properties of SAA on the vascular endothelium.