The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

Peptidyl prolyl isomerases (PPIases) are proteins belonging to the immunophilin family and are characterised by their cis-trans isomerization activity at the X-Pro peptide bond, in addition to their tetratricopeptide repeat (TPR) domain, important for interaction with the molecular chaperone, Hsp90. Due to this unique structure these proteins are able to facilitate protein-protein interactions which can impact significantly on a range of cellular processes such as cell signalling, differentiation, cell cycle progression, metabolic activity and apoptosis. Malfunction and/or dysregulation of most members of this class of proteins promotes cellular damage and tissue/organ failure, predisposing to ageing and age-related diseases. Many individual genes within the PPIase family are associated with several age-related diseases including cardiovascular diseases (CVDs), atherosclerosis, type II diabetes (T2D), chronic kidney disease (CDK), neurodegeneration, cancer and age-related macular degeneration (AMD), in addition to the ageing process itself. This review will focus on the different roles of PPIases, and their therapeutic/biomarker potential in these age-related vascular diseases.

The use of water soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle invasive bladder cancer

Objectives: To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods: Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings: Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion: The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.

Aging Behavior of YAl2p/Mg-14Li-1Al Composite

YAl2p/Mg-14Li-1Al composite was made by a stir-casting technique. The aging behavior of the composite was investigated using hardness test, differential scanning calorimetry, and X-ray diffraction. The results show that the microhardness variations of both the matrix alloy and its composite are related to the precipitation and decomposition of θ-MgLi2Al phase. The strengthening of the composite is from the addition of YAl2 particulates and the precipitation in matrix alloy. The former contribution is stable, but the latter is unstable and depends on the aging behavior. The addition of YAl2 particulates delays occurring of the aging behavior of composite.

Sclera as a Surrogate Marker for Determining AGE-Modifications in Bruch's Membrane Using a Raman Spectroscopy-Based Index of Aging

PURPOSE. Raman spectroscopy is an effective probe of advanced glycation end products (AGEs) in Bruch's membrane. However, because it is the outermost layer of the retina, this extracellular matrix is difficult to analyze in vivo with current technology. The sclera shares many compositional characteristics with Bruch's membrane, but it is much easier to access for in vivo Raman analysis. This study investigated whether sclera could act as a surrogate tissue for Raman-based investigation of pathogenic AGEs in Bruch's membrane.

METHODS. Human sclera and Bruch's membrane were dissected from postmortem eyes (n = 67) across a wide age range (33-92 years) and were probed by Raman spectroscopy. The biochemical composition, AGEs, and their age-related trends were determined from data reduction of the Raman spectra and compared for the two tissues.

RESULTS. Raman microscopy demonstrated that Bruch's membrane and sclera are composed of a similar range of biomolecules but with distinct relative quantities, such as in the heme/collagen and the elastin/collagen ratios. Both tissues accumulated AGEs, and these correlated with chronological age (R(2) = 0.824 and R(2) = 0.717 for sclera and Bruch's membrane, respectively). The sclera accumulated AGE adducts at a lower rate than Bruch's membrane, and the models of overall age-related changes exhibited a lower rate (one-fourth that of Bruch's membrane) but a significant increase with age (P <0.05).

CONCLUSIONS. The results suggest that the sclera is a viable surrogate marker for estimating AGE accumulation in Bruch's membrane and for reliably predicting chronological age. These findings also suggest that sclera could be a useful target tissue for future patient-based, Raman spectroscopy studies. (Invest Ophthalmol Vis Sci 2011;52:1593-1598) DOI:10.1167/iovs.10-6554

Sum-Rate and Power Scaling of Massive MIMO Systems with Channel Aging

This paper investigates the achievable sum-rate of massive multiple-input multiple-output (MIMO) systems in the presence of channel aging. For the uplink, by assuming that the base station (BS) deploys maximum ratio combining (MRC) or zero-forcing (ZF) receivers, we present tight closed-form lower bounds on the achievable sum-rate for both receivers with aged channel state information (CSI). In addition, the benefit of implementing channel prediction methods on the sum-rate is examined, and closed-form sum rate lower bounds are derived. Moreover, the impact of channel aging and channel prediction on the power scaling law is characterized. Extension to the downlink scenario and multi-cell scenario are also considered. It is found that, for a system with/without channel prediction, the transmit power of each user can be scaled down at most by 1= p M (where M is the number of BS antennas), which indicates that aged CSI does not degrade the power scaling law, and channel prediction does not enhance the power scaling law; instead, these phenomena affect the achievable sum-rate by degrading or enhancing the effective signal to interference and noise ratio, respectively.

Effect of channel aging on the sum rate of uplink massive MIMO systems

This paper investigates the achievable sum-rate of uplink massive multiple-input multiple-output (MIMO) systems considering a practical channel impairment, namely, aged channel state information (CSI). Taking into account both maximum ratio combining (MRC) and zero-forcing (ZF) receivers at the base station, we present tight closed-form lower bounds on the sum-rate for both receivers, which provide efficient means to evaluate the sum-rate of the system. More importantly, we characterize the impact of channel aging on the power scaling law. Specifically, we show that the transmit power of each user can be scaled down by 1/√(M), which indicates that aged CSI does not affect the power scaling law; instead, it causes only a reduction on the sum rate by reducing the effective signal-to-interference-and-noise ratio (SINR).