Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNF, sTNFRI and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality

Photocatalytic Nanolithography of Self-Assembled Monolayers and Proteins

Self-assembled monolayers of alkylthiolates on gold and alkylsilanes on silicon dioxide have been patterned photocatalytically on sub-100 nm length-scales using both apertured near-field and apertureless methods. Apertured lithography was carried out by means of an argon ion laser (364 nm) coupled to cantilever-type near-field probes with a thin film of titania deposited over the aperture. Apertureless lithography was carried out with a helium–cadmium laser (325 nm) to excite titanium-coated, contact-mode atomic force microscope (AFM) probes. This latter approach is readily implementable on any commercial AFM system. Photodegradation occurred in both cases through the localized photocatalytic degradation of the monolayer. For alkanethiols, degradation of one thiol exposed the bare substrate, enabling refunctionalization of the bare gold by a second, contrasting thiol. For alkylsilanes, degradation of the adsorbate molecule provided a facile means for protein patterning. Lines were written in a protein-resistant film formed by the adsorption of oligo(ethylene glycol)-functionalized trichlorosilanes on glass, leading to the formation of sub-100 nm adhesive, aldehyde-functionalized regions. These were derivatized with aminobutylnitrilotriacetic acid, and complexed with Ni2+, enabling the binding of histidine-labeled green fluorescent protein, which yielded bright fluorescence from 70-nm-wide lines that could be imaged clearly in a confocal microscope

Taking a hard line with biotemplating: cobalt-doped magnetite magnetic nanoparticle arrays.

Rapid advancements made in technology, and the drive towards miniaturisation, means that we require reliable, sustainable and cost effective methods of manufacturing a wide range of nanomaterials. In this bioinspired study, we take advantage of millions of years of evolution, and adapt a biomineralisation protein for surface patterning of biotemplated magnetic nanoparticles (MNPs). We employ soft-lithographic micro-contact printing to pattern a recombinant version of the biomineralisation protein Mms6 (derived from the magnetotactic bacterium Magnetospirillum magneticum AMB-1). The Mms6 attaches to gold surfaces via a cysteine residue introduced into the N-terminal region. The surface bound protein biotemplates highly uniform MNPs of magnetite onto patterned surfaces during an aqueous mineralisation reaction (with a mean diameter of 90 ± 15 nm). The simple addition of 6% cobalt to the mineralisation reaction maintains the uniformity in grain size (with a mean diameter of 84 ± 14 nm), and results in the production of MNPs with a much higher coercivity (increased from ≈156 Oe to ≈377 Oe). Biotemplating magnetic nanoparticles on patterned surfaces could form a novel, environmentally friendly route for the production of bit-patterned media, potentially the next generation of ultra-high density magnetic data storage devices. This is a simple method to fine-tune the magnetic hardness of the surface biotemplated MNPs, and could easily be adapted to biotemplate a wide range of different nanomaterials on surfaces to create a range of biologically templated devices