Fluorinated Phthalocyanine/Silver Nanoconjugates for Multifunctional Biological Applications

In this study, a new phthalonitrile derivative namely 4-[(2,4-difluorophenyl)ethynyl]phthalonitrile ( 1 ) and its metal phthalocyanines ( 2 and 3 ) were synthesized. The resultant compounds were conjugated to silver nanoparticles and characterized using transmission electron microscopy (TEM) images. The biological properties of compounds ( 1 – 3 ), their nanoconjugates ( 4 – 6 ), and silver nanoparticles ( 7 ) were examined for the first time in this study. The antioxidant activities of biological candidates ( 1 – 7 ) were studied by applying the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The highest antioxidant activity was obtained 97.47 % for 200 mg/L manganese phthalocyanine-silver nanoconjugates ( 6 ). The antimicrobial and antimicrobial photodynamic therapy (APDT) activities of biological candidates ( 1 – 7 ) were examined using a micro-dilution assay. The highest MIC value was obtained 8 mg/L for nanoconjugate 6 against E. hirae. The studied compounds and their silver nanoconjugates exhibited high APDT activities against all the studied microorganisms. The most effective APDT activities were obtained 4 mg/L for nanoconjugates ( 5 and 6 ) against L. pneumophila and E. hirae, respectively. All the studied biological candidates displayed high cell viability inhibition activities against E. coli cell growth. The biofilm inhibition activities of the tested biological candidates were also investigated against S. aureus and P. Aeruginosa. Biological candidates ( 1 – 6 ) can be considered efficient metal nanoparticle-based materials for multi-disciplinary biological applications.     

Metal Binding Antimicrobial Peptides in Nanoparticle Bio-functionalization: New Heights in Drug Delivery and Therapy

Probiotics and Antimicrobial Proteins - Peptides are considered very important due to the diversity expressed through their amino acid sequence, structure variation, large spectrum, and their...     

Feeding biology and resource partitioning of the Mullidae family members off the northeastern Levantine coast of Turkey

The introduction of invasive exotic species can have strong ecological impacts on the native biota, with direct consequences for commercial fisheries. Feeding ecology studies are among the primary sources for improving predictions related to community structures, for example, by revealing potential competitive interactions between native and invasive species. We compared the stomach contents and studied diet overlaps among a native (Mullus barbatus) and two invasive (Upeneus moluccensis and U. pori) mullid species, collected off the coasts of the northeastern Levantine where invasive mullids have been part of the ecosystem for more than half a century. We also assessed the effect of sex, sampling period, depth and size on stomach contents. Schoener’s index indicated significant diet overlaps between U. moluccensis–U. pori and U. moluccensis–M. barbatus. Diets of U. pori and M. barbatus did not significantly overlap, which was explained by their differing depth preferences. Assessment of stomach contents showed that Crustacea, specifically Decapoda, was the main prey group across the studied mullid species. Polychaeta was also of high importance in the diet of the native M. barbatus, but not for the two invasive Upeneus species. A trophic level analysis revealed the two invasive mullids to have a higher trophic level than the native species (U. moluccensis: 3.58, U. pori: 3.55 versus M. barbatus: 3.38). The lack of a clear separation in habitat and diet preferences documented here between native and invasive mullids may pose a risk for the persistence of the economically valuable native M. barbatus in the Mediterranean Sea.

     

Glutathione Encapsulation in Core-Shell Drug Nanocarriers (Polymersomes and Niosomes) Prevents Advanced Glycation End-products Toxicities

International Journal of Peptide Research and Therapeutics - The clinical application of some natural molecules in therapy is usually limited due to the lack of feasible delivery systems....     

Cytogenetic analysis of buccal cells from shoeworkers and pathology and anatomy laboratory workers exposed to n-hexane,toluene, methyl ethyl ketone and formaldehyde

People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (±SD) MN frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62±0.45%, 0.71±0.56% and 0.33±0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.     

Imputing Amino Acid Polymorphisms in Human Leukocyte Antigens

DNA sequence variation within human leukocyte antigen (HLA) genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC) makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC) region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C) and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1) loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals) and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals). We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918) with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes.     

Stereoselective synthesis of 1,2:4,5-di-O-isopropylidene-3-C-(5-phenyl-1,2,4-oxadiazol-3-yl)-beta-D-psicopyranose and its X-ray crystallographic analysis

In a novel procedure, when 3-O-benzoyl-3-C-(N-hydroxycarbamimidoyl)-1,2:4,5-di-O-isopropylidene-beta-D-psicopyranose (1) is treated with acetic anhydride, chloroacetyl chloride, propanic anhydride and benzoyl chloride, the 3-O-benzoyl group undergoes an intramolecular replacement reaction with neighbouring group participation and transfer resulting in a more stable conjugated system by the formation of a 1,2,4-oxadiazol ring. A possible mechanism is reported. The structure has been determined by spectroscopic data and X-ray crystallographic analysis.     

Oxidant-induced DNA damage by quartz in alveolar epithelial cells

Respirable quartz has recently been classified as a human carcinogen. Although, studies with quartz using naked DNA as a target suggest that formation of oxyradicals by particles may play a role in the DNA-damaging properties of quartz, it is not known whether this pathway is important for DNA damage in the target cells for quartz carcinogenesis, i.e. alveolar epithelial cells. Therefore, we determined in vitro DNA damage by DQ12 quartz particles in rat and human and alveolar epithelial cells (RLE, A549) using the single cell gel electrophoresis/comet assay. The radical generation capacity of quartz was analysed by electron spin resonance (ESR) and by immunocytochemical analysis of the hydroxyl radical-specific DNA lesion 8-hydroxydeoxyguanosine (8-OHdG) in the epithelial cells. Quartz particles as well as the positive control hydrogen peroxide, caused a dose-dependent increase in DNA strand breaks in both cell lines. DNA damage by quartz was significantly reduced in the presence of the hydroxyl-radical scavengers mannitol or DMSO. The involvement of hydroxyl radicals was further established by ESR measurements and was also demonstrated by the ability of the quartz to induce formation of 8-OHdG. In conclusion, our data show that quartz elicits DNA damage in rat and human alveolar epithelial cells and indicate that these effects are driven by hydroxyl radical-generating properties of the particles.     

Effects of Lead on the Activities of Antioxidant Enzymes in Watercress, <Emphasis Type="Italic">Nasturtium officinale</Emphasis> R. Br.

The aim of the present study is to evaluate the oxidative effects of lead with increased concentrations by the determination of antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase (AP)) and lipid peroxidation levels in the stem and leaves of watercress (Nasturtium officinale R. Br.) which was exposed to lead acetate, Pb (CH₃COOH)₂ regime with concentrations of 0, 50, 100, 200, 250, and 500 mg/L Pb in a hydroponic culture. After 14 days, accumulation of lipid peroxidation in stems and leaves and changes in activity of antioxidant enzymes were determined spectrophotometrically. The maximum accumulation was observed in the highest concentration group. In this group, lipid peroxidation levels were three times higher than the control group in the stem and leaves. The highest induction in SOD and GR activities were determined at 200 mg/L Pb group in stem, whereas CAT and AP activities were higher than other groups at the concentration of 250 and 100 mg/L Pb, respectively. The increase in CAT activity was found to be greater than GR, SOD, and AP activities in stems of watercress under Pb treatment. Both lead accumulation and antioxidant enzyme responses were higher in stems than in leaves. The results of the present study suggested that the induction in antioxidant responses could be occurring as an adaptive mechanism to the oxidative potential of lead accumulation.     

Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes

A variant of the PTPN22 gene, 1858C/T, is associated with an increased risk for the development of a wide array of autoimmune disorders. It is known that the protein tyrosine phosphatase Lyp encoded by this gene has an inhibitory effect on the proximal TCR signaling pathways. However, the consequences of carrying this variant and the mechanism by which it contributes to the development of autoimmunity are poorly understood. In this study, we demonstrate that homozygosity for this variant results in a profound deficit in T cell responsiveness to Ag stimulation. Heterozygosity for the variant allele is associated with reduced responsiveness of CD4+ memory T cells, characterized by diminished calcium mobilization, expression of CD25, and IL-10 production upon TCR stimulation. Additionally, the presence of the variant allele is associated with an increase in circulating memory T cells. We further demonstrate that these effects are not limited to the T cell compartment. Individuals with the variant allele have fewer memory B cells and these cells display a reduced response to stimulation via the BCR indicative of a B cell intrinsic defect. By identifying an immunologic phenotype in healthy subjects which correlates with the PTPN22 1858C/T genotype, we can now explore specific hypotheses regarding pathogenesis of diseases associated with the PTPN22 1858T variant.