Correlation of the amino-acid sequence and the 3D structure of the functional domain of EmaA from Aggregatibacter actinomycetemcomitans

Adhesion to collagen is an important virulence determinant for the periodontal pathogen Aggregatibacter actinomycetemcomitans. Binding to collagen is mediated by the extracellular-matrix protein adhesin-A (EmaA). EmaA is a homotrimeric autotransporter protein that forms flexible antenna-like appendages on the bacterium surface. An ellipsoidal structure at the distal end of the appendage, composed of three subdomains, contains the functional domain of the molecule. A correlation between amino-acid sequence and subdomain structure (SI and SII) was proposed based on an analysis of the volume/molecular weight ratio. EmaA from three mutant strains (deletions of amino-acids 70-206 and 70-386 and a substitution mutation G162S) has been studied by electron microscopy to test this hypothesis. 3D structures were analyzed using single-axis tilt tomography of negatively stained preparations of bacteria combined with subvolume averaging. Additionally, a large number of 2D images of the apical domain of the adhesins from the mutants were extracted from micrographs of the bacterial surface, aligned and classified. The combined data showed that amino-acids 70-206 localize to subdomain SI and 70-386 comprise subdomains SI and SII. Moreover, we showed that the substitution mutation G162S, which abolishes collagen binding activity, does not affect the overall structural integrity of the functional domain. However, the structure of subdomain SI in this mutant is slightly altered with respect to the wild-type strain. These data also have allowed us to interpret the architectural features of each subdomain of EmaA in more detail and to correlate the 3D structure of the functional domain of EmaA with the amino-acid sequence.     

The Effects of Synbiotic Supplementation on Pregnancy Outcomes in Gestational Diabetes

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidative actions. This study was designed to evaluate the effects of synbiotic administration on biomarkers of inflammation, oxidative stress, and pregnancy outcomes among gestational diabetic (GDM) women. This randomized, double-blind, placebo-controlled clinical trial was carried out among 60 subjects with GDM who were not on oral hypoglycemic agents. Patients were randomly assigned to consume either one synbiotic capsule containing Lactobacillus acidophilus strain T16 (IBRC-M10785), L. casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 10⁹ CFU/g each) plus 800 mg inulin (HPX) (n = 30) or placebo (n = 30) for 6 weeks. Compared with the placebo, synbiotic supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (? 1.9 ± 4.2 vs. +1.1 ± 3.5 mg/L, P = 0.004), plasma malondialdehyde (MDA) (? 0.1 ± 0.6 vs. + 0.3 ± 0.7 μmol/L, P = 0.02), and significantly increased total antioxidant capacity (TAC) (+ 70.1 ± 130.9 vs. ? 19.7 ± 124.6 mmol/L, P = 0.009) and total glutathione (GSH) levels (+ 28.7 ± 61.5 vs. ? 14.9 ± 85.3 μmol/L, P = 0.02). Supplementation with synbiotic had a significant decrease in cesarean section rate (16.7 vs. 40.0%, P = 0.04), lower incidence of hyperbilirubinemic newborns (3.3 vs. 30.0%, P = 0.006), and newborns’ hospitalization (3.3 vs. 30.0%, P = 0.006) compared with the placebo. Synbiotic supplementation did not affect plasma nitric oxide (NO) levels and other pregnancy outcomes. Overall, synbiotic supplementation among GDM women for 6 weeks had beneficial effects on serum hs-CRP, plasma TAC, GSH, and MDA; cesarean section; incidence of newborn’s hyperbilirubinemia; and newborns’ hospitalization but did not affect plasma NO levels and other pregnancy outcomes. http://www.irct.ir: www.irct.ir: IRCT201704205623N108     

Distribution of bacterial contamination in a teaching hospital in Tehran - a special focus on Staphylococcus aureus

There are documents that confirm the cycle of bacterial transmission between patients, staff, and the inanimate environment. The environment may have more effect on intensive care units (ICUs), because the patients who require intensive care have unstable clinical conditions and are more sensitive to infections. The aim of this study was to determine the prevalence of bacteria in air and inanimate surface in the ICUs and to compare the microbial levels to standard levels.Air and inanimate surface in the four ICUs of a teaching hospital underwent weekly surveillance by means of air sampler and swabs for a period of six-month. Total bacterial counts were evaluated onto trypticase soy agar and mannitol salt agar (MSA).A total of 725 samples [air (168) and inanimate surfaces (557)] were collected. The total mean ± SD CFU/m3 of airborne bacteria in all of the ICUs were 115.93 ± 48.04. The most common bacteria in air of the ICUs were Gram-positive cocci (84.2%). The total mean ± SD airborne of Staphylococcus aureus was 12.10±8.11 CFU/m3. The highest levels of S. aureus contamination were found in ventilators and bed ledges. More suitable disinfection of hospital environments and monthly rotation in utilization of the various disinfectant agents are needed for the prevention of airborne and inanimate transmission of S. aureus.     

A Chimeric protein of CFA/I,CS6 subunits and LTB/STa toxoid protects immunized mice against enterotoxigenic Escherichia coli

Enterotoxigenic Escherichia Coli (ETEC) strains are the commonest bacteria causing diarrhea in children in developing countries and travelers to these areas. Colonization factors (CFs) and enterotoxins are the main virulence determinants in ETEC pathogenesis. Heterogeneity of CFs is commonly considered the bottleneck to developing an effective vaccine. It is believed that broad spectrum protection against ETEC would be achieved by induced anti‐CF and anti‐enterotoxin immunity simultaneously. Here, a fusion antigen strategy was used to construct a quadrivalent recombinant protein called 3CL and composed of CfaB, a structural subunit of CFA/I, and CS6 structural subunits, LTB and STa toxoid of ETEC. Its anti‐CF and antitoxin immunogenicity was then assessed. To achieve high‐level expression, the 3CL gene was synthesized using E. coli codon bias. Female BALB/C mice were immunized with purified recombinant 3CL. Immunized mice developed antibodies that were capable of detecting each recombinant subunit in addition to native CS6 protein and also protected the mice against ETEC challenge. Moreover, sera from immunized mice also neutralized STa toxin in a suckling mouse assay. These results indicate that 3CL can induce anti‐CF and neutralizing antitoxin antibodies along with introducing CFA/I as a platform for epitope insertion.

     

The Effects of Probiotic Supplementation on Genetic and Metabolic Profiles in Patients with Gestational Diabetes Mellitus: a Randomized,Double-Blind,Placebo-Controlled Trial

This study was carried out to evaluate the effects of probiotic supplementation on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM) who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 patients with GDM. Participants were randomly divided into two groups to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum (2 × 10⁹ CFU/g each) (n = 24) or placebo (n = 24) for 6 weeks. Probiotic intake upregulated peroxisome proliferator-activated receptor gamma (P = 0.01), transforming growth factor beta (P = 0.002) and vascular endothelial growth factor (P = 0.006), and downregulated gene expression of tumor necrosis factor alpha (P = 0.03) in peripheral blood mononuclear cells of subjects with GDM. In addition, probiotic supplementation significantly decreased fasting plasma glucose (β, − 3.43 mg/dL; 95% CI, − 6.48, − 0.38; P = 0.02), serum insulin levels (β, − 2.29 μIU/mL; 95% CI, − 3.60, − 0.99; P = 0.001), and insulin resistance (β, − 0.67; 95% CI, − 1.05, − 0.29; P = 0.001) and significantly increased insulin sensitivity (β, 0.009; 95% CI, 0.004, 0.01; P = 0.001) compared with the placebo. Additionally, consuming probiotic significantly decreased triglycerides (P = 0.02), VLDL-cholesterol (P = 0.02), and total-/HDL-cholesterol ratio (P = 0.006) and significantly increased HDL-cholesterol levels (P = 0.03) compared with the placebo. Finally, probiotic administration led to a significant reduction in plasma malondialdehyde (P < 0.001), and a significant elevation in plasma nitric oxide (P = 0.01) and total antioxidant capacity (P = 0.01) was observed compared with the placebo. Overall, probiotic supplementation for 6 weeks to patients with GDM had beneficial effects on gene expression related to insulin and inflammation, glycemic control, few lipid profiles, inflammatory markers, and oxidative stress.

     

Arsenate phytoextraction abilities of one-year-old tree species and its effects on the nutritional element content in plant organs

Abstract

The aim of the study was to evaluate the As phytoextraction potential of four tree species: Acer pseudoplatanus L., Betula pendula Roth., Quercus robur L., and Ulmus laevis Pall. in light of their prospective use in the phytoremediation of arsenate [As(V)] contaminated soils. The content of nutritional elements: B, Ca, K, Mg, Na, Si, P, and S was also analyzed. The trees were grown for 1?month in hydroponic cultures (Knop medium) supplemented with As(V), (1?mM). The results showed that the highest As accumulation efficiency was characterized by B. pendula (BCF = 0.87) and Q. robur (BCF = 0.5). Betula pendula accumulated about 80% of As in its roots (TF = 0.22) whereas Q. robur accumulated more than 60% of As in its shoots (TF = 1.60). The other tree species accumulated significantly lower amounts of As, more than 60% of which collected in their shoots. As(V) phytoextraction led to a significantly lower level of P and S in the roots of all tested tree species. Betula pendula seems promising for phytostabilisation and Q. robur for phytoextraction of As(V) from contaminated soils. The obtained results confirm the accumulation and translocation of As(V), as well as the acquisition of nutritional elements by the selected tree species.     

EW-7197 prevents ulcerative colitis-associated fibrosis and inflammation

EW-7197 is a transforming growth factor-β type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.     

Modulation of anticonvulsant effects of cannabinoid compounds by GABA-A receptor agonist in acute pentylenetetrazole model of seizure in rat

Cannabinoid system plays an important role in controlling neuronal excitability and brain function. On the other hand, modulation of gamma-aminobutyric acid (GABA) transmission is one of the initial strategies for the treatment of seizure. The aim of the present study was to evaluate possible interaction between cannabinoidergic and GABAergic systems in pentylenetetrazole (PTZ)-induced acute seizure in rat. Drugs were administered by intracerebroventricular (i.c.v.) administration 20 min before a single intraperitoneal (i.p.) injection of PTZ and the latency to the first generalized tonic-clonic seizure was measured. Both the cannabinoid receptor agonist WIN55212-2 (10, 30, 50 and 100 μg/rat) and the GABA-A receptor agonist isoguvacine (IGN; 10, 30 and 50 μg/rat) significantly increased the latency of seizure occurrence. Moreover, the fatty acid amide hydrolase inhibitor URB597 showed no anticonvulsive effect while the monoacyl glycerol lipase (MAGL) inhibitor URB602 (10, 50 and 100 μg/rat) protected rats against PTZ-induced seizure. Moreover, co-administration of IGN and cannabinoid compounds attenuated the anticonvulsant action of both WIN55212-2 and IGN in this model of seizure. Our data suggests that exogenous cannabinoid WIN55212-2 and MAGL inhibitor URB602 imply their antiseizure action in part through common brain receptorial system. Moreover, the antagonistic interaction of cannabinoids and IGN in protection against PTZ-induced seizure could suggest the involvement of GABAergic system in their anticonvulsant action.     

Utilizing Waste Cable Wires for High‐Performance Fiber‐Based Hybrid Supercapacitors: An Effective Approach to Electronic‐Waste Management

In recent years, electronic waste (e‐waste) such as old cable wires, fans, circuit boards, etc., can be often seen in large piles of leftover in dumping yards. Employing these e‐waste sources for energy storage devices not only increases the economic value but also decreases the reliance on fossil fuels. In this context, waste cable wires are utilized to obtain precious copper (Cu) fibers and used as a cost‐effective current collector for the fabrication of fiber‐based hybrid supercapacitor (FHSC). With the braided Cu fibers, forest‐like nickel oxide nanosheet grafted carbon nanotube coupled copper oxide nanowire arrays (NiO NSs@CNTs@CuO NWAs/Cu fibers) are designed via simple wet‐chemical approaches. As a battery‐type material, the forest‐like NiO NSs@CNTs@CuO NWAs/Cu fiber electrode shows superior electrochemical properties including high specific capacity (230.48 mA h g^?1) and cycling stability (82.72%) in aqueous alkaline electrolyte. Moreover, a solid‐state FHSC is also fabricated using forest‐like NiO NSs@CNTs@CuO NWAs/Cu fibers as a positive electrode and activated carbon coated carbon fibers as a negative electrode with a gel electrolyte, which also shows a higher energy and power densities of 26.32 W h kg^?1 and 1218.33 W kg^?1, respectively. The flexible FHSC is further employed as an energy source for various electronic gadgets, demonstrating its suitability for wearable applications.     

Assessment of the interaction procedure between Pt(IV) prodrug [Pt(5,5′-dmbpy)Cl4 and human serum albumin: Combination of spectroscopic and molecular modeling technique

In this study, a cytotoxic Pt(IV) complex [Pt(5,5′-dmbpy)Cl₄ (5,5′-dmbpy is 5,5′-dimethyl-2,2′-bipyridine) was selected to investigate its affinity to human serum albumin (HSA) by spectroscopy and molecular docking methods. This complex has a bidentate nitrogen donor ligand with four chloride anions attached to a Pt(IV) metal in a distorted octahedral environment. The ?uorescence data showed this complex quench the intrinsic ?uorescence of HSA through a static quenching mechanism. The binding constant (K_b) and the number of binding sites (n) were obtained based on the results of fluorescence measurements. UV–vis, circular dichroism spectroscopy, and three-dimensional fluorescence spectroscopy proved that the Pt(IV) complex could slightly change the secondary structure of protein. Thermodynamic parameters show that the Pt(IV) complex binds to HSA through electrostatic and Vander Waals interactions with one binding site. The molecular docking results confirmed the spectroscopic results and showed that Pt(IV) complex is embedded into subdomain IIA of protein. The aim of this study is to describe the performance of effective anti-cancer drugs when faced with proteins such as HSA.