Aligned nanofibres made of poly(3-hydroxybutyrate) grafted to hyaluronan for potential healthcare applications

In this work, a hybrid copolymer consisting of poly(3-hydroxybutyrate) grafted to hyaluronic acid (HA) was synthesised and characterised. Once formed, the P(3HB)-g-HA copolymer was soluble in water allowing a green electrospinning process. The diameters of nanofibres can be tailored by simply varying the Mw of polymer. The optimization of the process allowed to produce fibres of average diameter in the range of 100-150 nm and low polydispersity. The hydrophobic modification has not only increased the fibre diameter, but also the obtained layers were homogenous. At the nanoscale, the hybrid copolymer exhibited an unusual hairy topography. Moreover, the hardness and tensile properties of the hybrid were found to be superior compared to fibres made of unmodified HA. Particularly, this reinforcement was achieved at the longitudinal direction. Additionally, this work reports the use in the composition of a water-soluble copolymer containing photo cross-linkable moieties to produce insoluble materials post-electrospinning. The derivatives as well as their nanofibrous mats retain the biocompatibility of the natural polymers used for the fabrication

Peripheral circadian clocks are diversely affected by adrenalectomy

<p>Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (<i>Bmal1, Per1-3, Cry1, RevErbα, Rora</i>), clock-output genes (<i>Dbp, E4bp4</i>) and a glucocorticoid- and clock-controlled gene (<i>Gilz</i>) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on the level of <i>Per1</i> mRNA in VAT, liver and jejunum, but not in kidney and splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of <i>Per2</i> in splenocytes and VAT, <i>Per3</i> in jejunum, <i>RevErbα</i> in VAT and <i>Dbp</i> in VAT, kidney and splenocytes, whereas the mRNA amounts of <i>Per1</i> and <i>Per2</i> in kidney and <i>Per3</i> in VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had minimal effects on <i>Rora</i> and <i>E4bp4</i> mRNAs. Adrenalectomy also resulted in decreased level of <i>Gilz</i> mRNA but did not alter the phase of its diurnal rhythm. Collectively, these findings suggest that adrenalectomy alters the mRNA levels of core clock genes and clock-output genes in peripheral organs and may cause tissue-specific modulations of their circadian profiles, which are reflected in changes of the amplitudes but not phases. Thus, the circulating corticosteroids are necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks in a tissue-specific manner.</p