A simple approach to constructing antibacterial and anti-biofouling nanofibrous membranes

<div><p>In this work, antibacterial and anti-adhesive polymeric thin films were constructed on polyacrylonitrile (PAN) nanofibrous membranes in order to extend their applications. Polyhexamethylene guanidine hydrochloride (PHGH) as an antibacterial agent and heparin (HP) as an anti-adhesive agent have been successfully coated onto the membranes <i>via</i> a layer-by-layer (LBL) assembly technique confirmed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), energy-dispersive spectroscopy (EDS) and scanning electron microscopy (SEM). The antibacterial properties of LBL-functionalized PAN nanofibrous membranes were evaluated using the Gram-positive bacterium <i>Staphylococcus aureus</i> and the Gram-negative <i>Escherichia coli.</i> Furthermore, the dependence of the antibacterial activity and anti-biofouling performance on the number of layers in the LBL films was investigated quantitatively. It was found that these LBL-modified nanofibrous membranes possessed high antibacterial activities, easy-cleaning properties and stability under physiological conditions, thus qualifying them as candidates for anti-biofouling coatings.</p></div

Distribution of serum MBL levels in diabetic patients with different groups.

<p>The horizontal lines indicate mean levels. (A) Distribution of serum MBL levels in diabetic patients with DR and without DR; (B) Distribution of serum MBL levels in diabetic patients withvision-threatening diabetic retinopathy (VTDR) and without VTDR. P values refer to Mann-Whitney U tests for differences between groups.</p

Correlation between the serum MBL levels and other factors (a) Correlation between the serum MBL levels and HbA1c; (b) Correlation between the serum MBL levels and Hs-CRP.

<p>Correlation between the serum MBL levels and other factors (a) Correlation between the serum MBL levels and HbA1c; (b) Correlation between the serum MBL levels and Hs-CRP.</p

A separate histogram of serum MBL levels in diabetic patientsand normal controls.

<p>The horizontal lines in the top indicate mean levels.<i>P</i>values refer to Mann-Whitney <i>U</i> tests for differencesbetween groups.</p

Receiver operating characteristic (ROC) curves were utilized to evaluate the accuracy of markers to diagnoseDR or VDTR.

<p>(A) Receiver operator characteristic curve demonstrating sensitivity as a function of 1-specificity for diagnosing the DR based on the MBL, Hs-CRP, HbA1c anddiabetes duration; (B) Receiver operator characteristic curve demonstrating sensitivity as a function of 1-specificity for diagnosing the VDTR based on the MBL, Hs-CRP, HbA1c anddiabetes duration.</p

Toward Infection-Resistant Surfaces: Achieving High Antimicrobial Peptide Potency by Modulating the Functionality of Polymer Brush and Peptide

Bacterial infection associated with indwelling medical devices and implants is a major clinical issue, and the prevention or treatment of such infections is challenging. Antimicrobial coatings offer a significant step toward addressing this important clinical problem. Antimicrobial coatings based on tethered antimicrobial peptides (AMPs) on hydrophilic polymer brushes have been shown to be one of the most promising strategies to avoid bacterial colonization and have demonstrated broad spectrum activity. Optimal combinations of the functionality of the polymer-brush-tethered AMPs are essential to maintaining long-term AMP activity on the surface. However, there is limited knowledge currently available on this topic. Here we report the development of potent antimicrobial coatings on implant surfaces by elucidating the roles of polymer brush chemistry and peptide structure on the overall antimicrobial activity of the coatings. We screened several combinations of polymer brush coatings and AMPs constructed on nanoparticles, titanium surfaces, and quartz slides on their antimicrobial activity and bacterial adhesion against Gram-positive and Gram-negative bacteria. Highly efficient killing of planktonic bacteria by the antimicrobial coatings on nanoparticle surfaces, as well as potent killing of adhered bacteria in the case of coatings on titanium surfaces, was observed. Remarkably, the antimicrobial activity of AMP-conjugated brush coatings demonstrated a clear dependence on the polymer brush chemistry and peptide structure, and optimization of these parameters is critical to achieving infection-resistant surfaces. By analyzing the interaction of polymer-brush-tethered AMPs with model lipid membranes using circular dichroism spectroscopy, we determined that the polymer brush chemistry has an influence on the extent of secondary structure change of tethered peptides before and after interaction with biomembranes. The peptide structure also has an influence on the density of conjugated peptides on polymer brush coatings and the resultant wettability of the coatings, and both of these factors contributed to the antimicrobial activity and bacterial adhesion of the coatings. Overall, this work highlights the importance of optimizing the functionality of the polymer brush to achieve infection-resistant surfaces and presents important insight into the design criteria for the selection of polymers and AMPs toward the development of potent antimicrobial coating on implants

DataSheet1_Understanding inter-individual variability in pharmacokinetics/pharmacodynamics of aripiprazole in children with tic disorders: Individualized administration based on physiological development and CYP2D6 genotypes.docx

Objective: This study aims to develop a combined population pharmacokinetic (PPK) model for aripiprazole (ARI) and its main active metabolite dehydroaripiprazole (DARI) in pediatric patients with tic disorders (TD), to investigate the inter-individual variability caused by physiological and genetic factors in pharmacokinetics of ARI and optimize the dosing regimens for pediatric patients.Methods: A prospective PPK research was performed in Chinese children with TD. Totally 84 patients aged 4.83–17.33 years were obtained for the pharmacokinetic analysis. 27 CYP2D6 and ABCB1 gene alleles were detected. Moreover, the clinical efficacy was evaluated according to reduction rate of Yale Global Tic Severity Scale (YGTSS) score at the 12th week comparing with the baseline. Monte Carlo simulations were used to evaluate and optimize dosing regimens.Results: The PPK model was established to predict the concentrations of ARI and DARI. Body weight and CYP2D6 genotype were the significant covariates affecting the clearance of ARI. The DARI/ARI metabolic ratios (MRs) of AUC24h, Cmin and Cmax at the steady state of results were ultra-rapid metabolizers (UMs) > normal metabolizers (NMs) > intermediated metabolizers (IMs). MRs could be used to distinguish UMs or IMs from other patients. The best predictor of clinical efficacy for TD was the trough concentration of ARI and the cut-off point was 101.636 ng/ml.Conclusion: The pharmacokinetics of ARI and DARI in pediatric TD were significantly influenced by body weight and CYP2D6 genotype. Individualized dosing regimens were recommended for pediatric patients with TD to ensure clinical efficacy.</p

Global expression profiling and pathway analysis of mouse mammary tumor reveals strain and stage specific dysregulated pathways in breast cancer progression

<p>It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.</p

Additional file 2: Figure S2. of Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling

Overexpressing CLCA2 impairs NPC cell migration and silencing CLCA2 promotes NPC cell migration ability in vitro. (PDF 492 kb

Additional file 1: FigureS1. of Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling

Knockdown of CLCA2 promotes the growth in NPC cells in vitro. (PDF 464 kb