Designing an immunoinformatic vaccine for peri-implantitis using a structural biology approach

ObjectivesPeri-implantitis is a destructive inflammatory process that affects the soft and hard tissues around dental implants. porphyromonas gingivalis, an anaerobic gram-negative bacterium, appears to be the main culprit. Since there is no efficient and specific vaccine to treat peri-implantitis, the goal of our research has been to develop a multi-epitope vaccination utilizing an immunoinformatics approach that targeted P. gingivalis type I fim A.Materials and methodsP. gingivalis peptides 6JKZ and 6KMF are suitable for vaccine development. B- and T-cell epitopes from 6KMF and 6JKZ were detected and evaluated based on critical factors to produce a multi-epitope vaccine construct. It was assessed based on allergenicity, antigenicity, stability. The vaccine's dual major histocompatibility complex (MHC-I and MHC-II) binding epitopes allowed it to reach a larger population. P. gingivalis fimbriae induce immune subversion through TLR -CXCR4 receptor complex pathway. The ClusPro 2.0 server was used to do the molecular docking using TLR2 - CXCR4 and vaccine epitopes as receptor and ligand respectively.ResultsThe designed vaccine was non-allergenic and had a high antigenicity, solubility, and stability. The 3D structure of the vaccine revealed strong interaction with CXCR4(TLR2) using molecular docking. The vaccine-CXCR4 interface was more consistent, possibly because the vaccination has a higher affinity for the CXCR4-TLR2 complex.ConclusionThis study details the vaccine's distinct and sustained interaction with the CXCR4(TLR2) immunological receptor and its consistent and effective utterance in the bacterial system. As a result, our vaccine formulation will evoke a significant memory response and induce an adaptive immune response against P. gingivalis.     

Multilocus enzyme electrophoresis analysis of Trypanosoma cruzi isolates from a geographically restricted endemic area for Chagas' disease in Argentina

A set of 65 Trypanosoma cruzi stocks from dogs, opossums, insect vectors and humans was isolated in a geographically restricted endemic area for Chagas' disease in Argentina and was analysed by multilocus enzyme electrophoresis for 15 loci. The results show that at least five multilocus genotypes (clonets) circulate in the study area, one belonging to T. cruzi IIe, one to T. cruzi IId and three clonets belonging to T. cruzi I; and they confirm the presence of these lineages in the country. The three clonets attributed to T. cruzi I were identical to each other for all loci except for Sod-2, where three different patterns were identified. These patterns suggest the presence of two homozygous genotypes and one heterozygous genotype. Our results also suggest association of clonet IIe with dogs, clonet IId with humans and the three T. cruzi I clonets with Didelphis albiventris. On the other hand, there was no significant association between Triatoma infestans and any particular clonet circulating in the area. These findings are consistent with the hypothesis of natural selection, from mixed populations of T. cruzi in vectors, toward more restricted populations in mammals. The epidemiological implications of the possible selection of different clonets by different mammal hosts and the significance of two homozygous genotypes and one heterozygous genotype for the Sod-2 locus are discussed.     

Theoretical studies of biliverdin: energetics of the reduction pathways to bilirubin

Geometries and energies of formation of bilirubin formed by reduction of biliverdin via three meso carbon sites, the , and positions, have been calculated using semiempirical methods. It has been shown that -bilirubin with a ridge-tile conformation forms six intramolecular hydrogen bonds and is the most stable of the three above mentioned positions by at least 22 kcal mol^–1. Reduction pathways for -, - and -bilirubin formations from biliverdin are studied in detail. The roles of loss of conjugation and hydrogen bond formations in stability of different conformers have been discussed. -Bilirubin was fully optimized by using ab initio methods. Fine refinements of calculated results show excellent agreement with experimental results. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00894-002-0078-9.Electronic Supplementary Material available.     

Evolutionary profile of the family Calliphoridae,with notes on the origin of myiasis

The family Calliphoridae is a group of heterogenous calyptrate flies with a worldwide distribution including species of ecological, veterinary, medical, and forensic importance. Notorious for their parasitic habits, the larvae of many blowflies are characterised – like some other dipteran larvae – by their ability to develop in animal flesh. When parasitism affects a living host, it is termed “myiasis”. This has led the Calliphoridae to be considered as a pivotal family in its relationship with a man. Nevertheless, even after more than 50 years of research, the phylogenetic relationships among calliphorid subfamilies together with the evolutionary origin of myiasis remain unclear. In order to elucidate these problems, we constructed three phylogenetic trees by using nucleotide sequence data from cytochrome oxidase subunit one (COI), representing a mitochondrial conservative gene, and nuclear 28S subunit of ribosomal RNA gene (28S rRNA) in order to interpret the evolutionary profile of myiasis in the family Calliphoridae. The sequenced data represented species associated with ectoparasitic life-styles, either saprophagy or facultative and obligate parasitism. A total number of 50 accessions were collected for 28S rRNA, 56 for COI, and 38 for combined sequences phylogeny. Molecular Evolutionary Genetics Analysis (MEGA) software was used to align 2197 nucleotide positions of 28S rRNA and 1500 nucleotide positions of COI with a gap opening penalties and gap extension penalties equalling 20 and 0.1 respectively. The results reveal the non-monophyly of the family Calliphoridae despite the stable monophyletic status of the Chrysomyinae, Luciliinae, and Auchmeromyiinae. Also, our findings recommend ranking the Toxotarsinae as a separate family. Furthermore, comparative analysis of the phylogenetic trees shows that the habit of obligatory myiasis originated independently more than five times. This strengthens our hypothesis that the origin of eating fresh meat is a case of convergent evolution that has taken place after speciation events millions of years ago. Finally, estimating the divergence dates between lineages from molecular sequences provides a better chance of understanding their evolutionary biology.     

Synthesis of Novel α-l-Arabinopyranosides of β-Lactams with Potential Antimicrobial Activity

Synthetic routes toward the synthesis of some novel 1-(2,3,4-tri-O-acetyl-α-l-arabinopyranosyl)-azetidin-2-ones are described. Antimicrobial screening of three selected compounds revealed their activity against Bacillus subtilis and Escherichia coli.     

Grape response to salinity stress and role of iron nanoparticle and potassium silicate to mitigate salt induced damage under in vitro conditions

Grape softwood cuttings of Khoshnaw cultivar were cultured using tissue-culture methods to study the effect of iron nanoparticles and potassium silicate under salinity conditions during the 2015–2016 growing season. The treatments consisted of salinity stress (0, 50, and 100 mM NaCl), nanoparticles of iron (0, 0.08, and 0.8 ppm), and potassium silicate (0, 1, 2 mM). The results also showed that the application of iron nanoparticles and potassium silicate significantly increased the total protein content and reduced proline, enzymatic antioxidant activity and hydrogen peroxide. Salinity stress reduced membrane stability index while increased malondialdehyde content. Increase of membrane stability index and reduction of malondialdehyde content were obtained for 2 mM potassium silicate and 0.8 ppm iron nanoparticle. Iron and potassium silicate were shown to lower the sodium content and increase the potassium content under salinity-stress conditions. The highest ratio of sodium to potassium was observed in plants under salinity conditions (100 mM) treated with neither iron nanoparticles nor potassium silicate; conversely, the lowest ratio was achieved in plants treated with both 0.8 ppm iron nanoparticles with 1 mM and 2 mM potassium silicate under non-stress conditions. These results indicate that the application of micronutrients in stressful conditions is a suitable method to compensate for the negative effects of salinity stress. Tissue culture in this study was shown to be an economically efficient and applicable technique for producing grape softwood cuttings to be used in experiments.     

Nanoformulation of curcumin protects HUVEC endothelial cells against ionizing radiation and suppresses their adhesion to monocytes: potential in prevention of radiation-induced atherosclerosis

Objectives

To investigated the potential of a novel dendrosomal nanoformulation of curcumin (DNC) in blocking radiation-induced changes in irradiated human umbilical vein endothelial cells (HUVECs), and their adhesion to human THP-1 monocytoid cells.

Results

Co⁶⁰ gamma rays reduced viability, raised the expression of adhesion molecules, ICAM-1, VCAM-1 and E-selectin (mRNA and protein), augmented the adhesion of THP-1 cells to HUVECs, activated NF-κB binding, increased the release of pro-inflammatory cytokines (IL-6, IL-8 and MCP-1) and induced oxidative damage (reduced glutathione declined, while 8-OHdG and TBARS increased). 5 µM DNC significantly inhibited these radiation-induced changes, activated the Nrf-2 pathway, and effectively suppressed THP-1 adhesion to HUVECs, implicating p38 MAPK signaling.

Conclusion

DNC treatment is a potential preventive method against inflammation and vascular damage from ionizing radiation.

     

Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N?=?63) and those without (N?=?54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R?=?0.18; p?=?.08) and HOMA β (R?=??0.19; p?=?.09) as well as significant positive associations with total cholesterol (R?=?0.25; p?=?.02), LDL-cholesterol (R?=?0.25; p?=?.02), 25(OH)D (R?=?0.22; p?=?.04), albumin (R?=?0.30; p?<?.01) and IL1β (R?=?0.41; p?<?.01). Stepwise regression analysis also suggested that IL1β, leptin and albumin were the significant predictors of SPX. In summary, SPX levels modestly affect glucose and insulin sensitivity in pregnant women but is not associated with GDM and obesity. The significant association of SPX to ILβ warrants further investigation as to the role of SPX in immune modulation.