Optical features of the fluorophore azotobactin: Applications for iron sensing in biological fluids

Siderophores are bio‐organic ligands secreted by microbes to chelate and assimilate iron to meet their metabolic requirements. Siderophores and their analogs have tremendous therapeutic and analytical potential including the use as Fe (III) biosensors; however, only few practical applications have been realized. The aim of this study was the optical and biophysical characterization of the siderophore azotobactin (Az) secreted by the nitrogen‐fixing bacteria Azotobacter vinelandii. The peptide exhibited fluorescence in the visible range. Quantum yield and lifetime in excited state were measured to ascertain the sensitivity of the molecule as a fluorescent marker in biochemical assays. Its high affinity toward iron in the ferric state was demonstrated through fluorescence emission quenching studies. The accuracy of azotobactin as biosensing tool was determined by analyzing the levels of iron in biological fluids, particularly in human serum. Furthermore, it was demonstrated that it can be encapsulated in sol–gel matrices without significant loss of its fluorescence signal, thus enabling it suitable for adaptation to optical biosensor for Fe (III).     

Autophagic induction modulates splenic plasmacytoid dendritic cell mediated immune response in cerebral malarial infection model

Splenic plasmacytoid dendritic cells (pDC) possess the capability to harbor live replicative Plasmodium parasite. Isolated splenic pDC from infected mice causes malaria when transferred to naïve mice. Incomplete autophagic degradation might cause poor antigen processing and poor immune response. Induction of autophagic flux by rapamycin treatment led to better prognosis by boosting pDC centered immune response against the pathogen. Splenic pDC from rapamycin-treated infected mice, caused less parasitemia in naïve mice. The downregulation of adhesion with unaltered phagocytic potential of the cells post autophagic induction restricted excessive parasite burden within them. Rapamycin-treated pDC played a better role in antigen presentation. They showed higher expression of co-stimulatory molecules CD80, CD86, DEC205, MHCI. Rapamycin-treated pDC induced CD28 expression on CD8⁺ T cells and suppressed FasL level. This cells also influenced differentiation of effector, memory T cell population. The increase in IL10: TNFα ratio, Treg: Th17 ratio and lowering of myeloid DC: plasmacytoid DC ratio was observed. It shifted the overaggressive inflammation mediated Th1 pathway that is reported to incur host damage, to a better well-balanced cytokine profile exhibiting Th2 pathway. Autophagic flux induction within pDC proved to be beneficial in combating malarial pathogenicity.     

Polysaccharides from the brown seaweed Padina tetrastromatica: Characterization of a sulfated fucan

Sulfated fucans, the complex polysaccharides from brown seaweeds, possess various biological activities. To understand the structure activity relationship of sulfated fucans, we have investigated the structural features of one such polymer from Padina tetrastromatica using standard methods of carbohydrate structural analysis. We report a novel structural motif for this polymer. The average structure of this macromolecule that has a molecular mass of 25 kDa differs from the previous models in three respects. First, the core region of this macromolecule is composed primarily of α-(1 → 2)- and α-(1 → 3)-linked fucopyranosyl residues. Sulfate groups, when present are located at position 4 and 2 of fucosyl residues. Secondly, fucose and xylose is attached to this polymer to form branch points, one for every two residues within the chain. Finally, this macromolecule contained smaller amount of sulfate (0.21 mol of sulfate per mol of deoxyhexose).     

Understanding ageing effects using complexity analysis of foot–ground clearance during walking

Ageing influences gait patterns which in turn can affect the balance control of human locomotion. Entropy-based regularity and complexity measures have been highly effective in analysing a broad range of physiological signals. Minimum toe clearance (MTC) is an event during the swing phase of the gait cycle and is highly sensitive to the spatial balance control properties of the locomotor system. The aim of this research was to investigate the regularity and complexity of the MTC time series due to healthy ageing and locomotors' disorders. MTC data from 30 healthy young (HY), 27 healthy elderly (HE) and 10 falls risk (FR) elderly subjects with balance problems were analysed. Continuous MTC data were collected and using the first 500 data points, MTC mean, standard deviation (SD) and entropy-based complexity analysis were performed using sample entropy (SampEn) for different window lengths (m) and filtering levels (r). The MTC SampEn values were lower in the FR group compared to the HY and HE groups for all m and r. The HY group had a greater mean SampEn value than both HE and FR reflecting higher complexity in their MTC series. The mean SampEn values of HY and FR groups were found significantly different for m = 2, 4, 5 and r = (0.1–0.9) × SD, (0.3–0.9) × SD and (0.3–0.9) × SD, respectively. They were also significant difference between HE and FR groups for m = 4–5 and r = (0.3–0.7) × SD, but no significant differences were seen between HY and HE groups for any m and r. A significant correlation of SampEn with SD of MTC was revealed for the HY and HE groups only, suggesting that locomotor disorders could significantly change the regularity or the complexity of the MTC series while healthy ageing does not. These results can be usefully applied to the early diagnosis of common gait pathologies.     

Targeting epigenetic modifications as a potential therapeutic option for diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of visual impairment in adults of working age (20–65 years) in developed countries. The metabolic memory phenomena (persistent effect of a glycemic insult even after retrieved) associated with it has increased the risk of developing the complication even after the termination of the glycemic insult. Hence, the need for finding early diagnosis and treatment options has been of great concern. Epigenetic modifications which generally occur during the beginning stages of the disease are responsible for the metabolic memory effect. Therefore, the therapy based on the reversal of the associated epigenetic mechanism can bring new insight in the area of early diagnosis and treatment mechanism. This review discusses the diabetic retinopathy, its pathogenesis, current treatment options, need of finding novel treatment options, and different epigenetic alterations associated with DR. However, the main focus is emphasized on various epigenetic modifications particularly DNA methylation which are responsible for the initiation and progression of diabetic retinopathy and the use of different epigenetic inhibitors as a novel therapeutic option for DR.