Nanohybrids of Silver Particles Immobilized on Silicate Platelet for Infected Wound Healing

Silver nanoparticles supported on nanoscale silicate platelets (AgNP/NSP) possess interesting properties, including a large surface area and high biocide effectiveness. The nanohybrid of AgNP/NSP at a weight ratio 7/93 contains 5-nm Ag particles supported on the surface of platelets with dimensions of approximately 80×80×1 nm3. The nanohybrid expresses a trend of lower cytotoxicity at the concentration of 8.75 ppm Ag and low genotoxicity. Compared with conventional silver ions and the organically dispersed AgNPs, the nanohybrid promotes wound healing. We investigated overall wound healing by using acute burn and excision wound healing models. Tests on both infected wound models of mice were compared among the AgNP/NSP, polymer-dispersed AgNPs, the commercially available Aquacel, and silver sulfadiazine. The AgNP/NSP nanohybrid was superior for wound appearance, but had similar wound healing rates, vascular endothelial growth factor (VEGF)-A levels and transforming growth factor (TGF)-β1 expressions to Aquacel and silver sulfadiazine

Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies

Objective: Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Research Design and Methods: Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.Results: The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I-2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.Conclusions: A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate

Composition of nanoclay supported silver nanoparticles in furtherance of mitigating cytotoxicity and genotoxicity.

Silver nanoparticle (Ag-NP) is well known for its high antibacterial efficacy. However, its toxicity toward mammalian cells is still a concern in clinical applications. The aim of our study was to evaluate the composition effects of Ag-NP supported by silicate nanoplatelet (NSP) with respect to the cytotoxicity and genotoxicity, and was in reference to the poly (styrene-co-maleic anhydride)-supported Ag-NP (Ag-NP/SMA). The NSP at the geometric dimension of averaged 80 x 80 x 1 nm3 was prepared from the exfoliation of natural clays and used to support different weight ratio of Ag-NP. The supporting limitation of NSP on Ag-NP was below the weight ratio of 15/85 (Ag-NP to NSP), and the detached Ag-NP from the Ag-NP/NSP (30/70) and Ag-NP/SMA hybrids were observed by TEM. Ames test was performed to assess the mutagenic potential of different compositions of Ag-NP/NSP, only Ag-NP/NSP (30/70) and Ag-NP/SMA hybrids exhibited mutagenicity when the concentration was 1.09 ppm or higher. In viewing of cytotoxicity using MTT tests toward HaCaT cells, the IC30 of Ag-NP/NSP (1/99, 7/93 and 15/85) were 1416.7, 243.6, and 148.9 ppm respectively, while Ag-NP/SMA was 64.8 ppm. The IC30 of Ag-NP/NSP (1/99, 7/93 and 15/85) were at least 833, 78 and 7 folds higher than their corresponding minimum inhibitory concentrations (MIC) respectively, and whereas Ag-NP/SMA was 6.4 folds. The Ag-NP/NSP and Ag-NP/SMA hybrids had been further investigated for genotoxicity by chromosomal aberrations and in vivo micronucleus assay within the concentration at IC10 and IC30, only Ag-NP/SMA showed a higher frequency of chromosomal aberrations. Our findings indicated that the viability of utilizing the NSP to maintain Ag-NP for antimicrobial activity, and the high-surface area of NSP served as an excellent support for associating Ag-NP and consequently rendering the mitigation of the inherent toxicity of Ag-NP in clinical uses

Cytokine profile of wound healing.

<p>Serum levels of VEGF-A, TGF-β1 and IL-6 from mice of different treatment groups in both acute thermal injury at day 7 and excision wound at day 15 were examined by ELISA method.</p><p>Results are expressed as the mean (pg/ml) ± standard deviation (SD) from three independent experiments of each group.</p>*<p>Statistically significant as compared to the Staph group (<i>P</i><0.01, Student’s <i>t</i> test).</p

Cytotoxicity toward the human foreskin fibroblast (Hs68) cell line after 12 h of incubation with AgNP/NSP, polymer dispersed AgNP (Poly-Ag) and silver sulfadiazine (SS) using the MTT assay (a).

<p>The values are expressed as the mean ± SD from 4 independent experiments. DNA damage in Chinese hamster ovary (CHO) cells by the comet assay showed the average lengths of the cell tails after incubation with different concentrations of AgNP/NSP and Poly-Ag (b). Data are shown as the mean ± SD (at least 200 cell tails were counted in each sample). *<i>P</i><0.05 at each concentration, Student’s <i>t</i> test.</p

mRNA levels of <i>VEGF-A, TGF-β1</i> and <i>IL-6</i> in different treatment groups during wound healing.

<p>AgNP/NSP treatment also modulates the expression of cytokine mRNAs in wounded skin. The levels of <i>VEGF-A</i>, <i>TGF-β1</i> and <i>IL-6</i> mRNA expression from mice of different treatment groups in both acute thermal injury at day 7 (a) and excision wound at day 15 (b) were examined by RT-PCR. Relative band intensities of different groups were calculated by a densitometer and are demonstrated by the values under the bands. The data shown are representative of three independent experiments.</p

Wound healing rates on (a) acute burn model (b) excision wound model and the photographs of wound appearance on day 5 after (c) acute burn injury and (d) excision injury.

<p>The rate of infected wound healing was compared in animals treated with staphylococcus only (Staph), staphylococcus and NSP (Staph+NSP), staphylococcus and Poly-Ag (Staph+Poly-Ag), staphylococcus and AgNP/NSP (Staph+AgNP/NSP), staphylococcus and Aquacel® (Staph+AQ), staphylococcus and silver sulfadiazine (Staph+SS), and control (untreated). The results are expressed as the mean ± SD from three independent experiments in each group. *<i>P</i><0.05, comparison between AgNP/NSP and the other 6 groups at each time point; † <i>P</i><0.05, comparison between SS treatment with the untreated, Staph, Staph+NSP, and Staph+Poly-Ag groups; ‡ <i>P</i><0.05, comparison between AQ treatment with the untreated, Staph, Staph+NSP, and Staph+Poly-Ag groups; # <i>P</i><0.05, comparison between NSP treatment with untreated, Staph and Staph+Poly-Ag groups; § <i>P</i><0.05, comparison between Poly-Ag treatment with untreated and Staph groups. All the comparisons were confirmed by Student’s <i>t</i> test.</p