Real-world study on clinical outcomes of nucleos(t)ide analogues antiviral therapy in patients with chronic hepatitis B.

Nucleos(t)ide analogues (NAs) are widely used for antiviral therapy in patients with chronic hepatitis B (CHB), but real-world data on treatment patterns and long-term clinical outcomes are not always available. Using data from electronic medical records between January 2011 and December 2016 in Shanghai, China, we evaluated patient characteristics, treatment patterns and clinical outcomes in patients with CHB. There were 6688 patients in the study cohort. The incidences of cirrhosis and hepatocellular carcinoma (HCC) were 41.0‰ and 6.8‰ person-years, respectively. There were more cirrhosis and HCC cases among patients who had shorter NA treatment duration (<365 days), or who were less compliant (<80%). In addition, increased risk of cirrhosis and HCC was observed in patients who did not achieve hepatitis B surface antigen (HBsAg) loss/seroconversion. Moreover, patients with cirrhosis developed after antiviral treatments had a higher incidence of HCC (adjusted hazard ratio 15.86, 95% confidence interval 7.35-34.24). Good compliance with treatment and longer treatment duration significantly decreased the risk of developing cirrhosis and HCC. HBsAg loss seemed to be a protective factor for cirrhosis/HCC in NAs-treated patients with CHB, and cirrhosis was a confirmed risk factor for HCC development as expected.

Shape-controlled synthesis of NIR absorbing branched gold nanoparticles and morphology stabilization with alkanethiols.

Gold nanoparticles are ideal candidates for clinical applications if their plasmon absorption band is situated in the near infrared region (NIR) of the electromagnetic spectrum. Various parameters, including the nanoparticle shape, strongly influence the position of this absorption band. The aim of this study is to produce stabilized NIR absorbing branched gold nanoparticles with potential for biomedical applications. Hereto, the synthesis procedure for branched gold nanoparticles is optimized varying the different synthesis parameters. By subsequent electroless gold plating the plasmon absorption band is shifted to 747.2 nm. The intrinsic unstable nature of the nanoparticles' morphology can be clearly observed by a spectral shift and limits their use in real applications. However, in this article we show how the stabilization of the branched structure can be successfully achieved by exchanging the initial capping agent for different alkanethiols and disulfides. Furthermore, when using alkanethiols/disulfides with poly(ethylene oxide) units incorporated, an increased stability of the gold nanoparticles is achieved in high salt concentrations up to 1 M and in a cell culture medium. These achievements open a plethora of opportunities for these stabilized branched gold nanoparticles in nanomedicine.

Increased stability of mercapto alkane functionalized Au nanoparticles towards DNA sensing.

The use of gold nanoparticles (GNPs) in bioassays is often hampered by their colloidal stability. In this study, gold nanoparticles coated with different mercapto alkanes were investigated towards their stability. Hereto, the effects of the alkane chain length (5-11 methylene groups), the type of functional end-group (-OH or -COOH) and the amount of incorporated poly-ethylene oxide units (none, 3 or 6) on the GNP stabilization was evaluated. Based on these results, an optimal mercapto alkane (HS(CH(2))(11)PEO(6)COOH) was selected to increase the colloidal stability up to 2 M NaCl. Furthermore, it was proved that this mercapto alkane is ideally suited to enhance the stability of DNA functionalized GNPs in high electrolytic hybridization buffers. The effectiveness of these DNA functionalized GNPs was demonstrated in a sandwich assay using a surface plasmon resonance biosensor. The superior stability of these nanoparticles during hybridization may lead to enhanced biosensor technologies.

Chemical and biological characterization of thiol SAMs for neuronal cell attachment.

Cellular adhesion and growth on solid-state surfaces is the central theme in the development of cell-based biosensors and implantable medical devices. Suitable interface techniques must be applied to construct stable and well-organized thin films of biologically active molecules that would control the development of neuronal cells on chips. Peptides such as RGD fragments, poly-L-lysine (PLL), or basal lamina proteins, such as laminin or fibronectin, are often used in order to promote cellular adhesion on surfaces. In this paper we describe the characterization of several self-assembled monolayers (SAMs) for their ability to anchor a laminin-derived synthetic peptide, PA22-2, a peptide known to promote neuronal attachment and stimulate neurite outgrowth. We have evaluated the immobilization of PA22-2 onto 16-mercaptohexadecanoic acid, 4-maleimide-N-(11-undecyldithio)butanamide, and 2-(maleimide)ethyl-N-(11-hexaethylene oxide-undecyldithio)acetamide SAM functionalized Au substrates. The neuronal attachment and outgrowth have been evaluated in embryonic mouse hippocampal neuron cultures up to 14 days in vitro. Our results show that differences in the cell morphologies were observed on the surfaces modified with various SAMs, despite the minor differences in chemical composition identified using standard characterization tools. These different cell morphologies can most probably be explained when investigating the effect of a given SAM layer on the adsorption of proteins present in the culture medium. More likely, it is the ratio between the specific PA22-2 adsorption and nonspecific medium protein adsorption that controls the cellular morphology. Large amounts of adsorbed medium proteins could screen the PA22-2 sites required for cellular attachment.

Peptide-functionalized microfabricated structures for improved on-chip neuronal adhesion.

Extracellular, high signal-to-noise ratio recordings from electrogenic cells require a tight coupling between the cellular membrane and the recording electrode. Self assembled monolayers (SAMs) of alkanethiols functionalized with peptides were used in combination with micro- and nano-structured features on the sensor surface. This combination of surface chemistry and topography triggers a phagocytosis-like engulfment and ensures tight coupling. In this paper we report the results concerning usage of different SAMs and the influence of the peptide concentration towards cell adhesion and outgrowth. Later on, the optimized peptide functionalized SAMs were applied on micro- and nano-structured sensor surfaces. As a result, phagocytosis-like events could be shown using focused ion beam SEM and confocal fluorescence imaging.