that this synthetic cartilage may be a suitable implant for some situations, such as the deeper parts of the knee. He also wonders whether chondrocytes might be able to take up residence inside the synthetic network to produce a hybrid cartilage. But his potential applications are not limited to cartilage. He suspects that similar networks, with different proportions of aramid nanofibers, PVA and water, may be able to stand in for other soft tissues. Gene marker could identify sickle cell patients with highest risk of complications Researchers have found a genotype that could help identify sickle cell disease (SCD) patients at greatest risk of common, yet severe, complications of SCD. The findings were presented at the American Physiological Society’s Physiological and Pathophysiological Consequences of Sickle Cell Disease conference in Washington, D.C.m in November. The chronic breakdown of red blood cells (haemolysis) is a hallmark of SCD that increases during times of illness. Haemolysis leads to the release of haemoglobin – and a protein that binds with it called haptoglobin – that increase a patient’s chances of developing acute chest syndrome (ACS). “ACS is defined broadly as increased respiratory effort, fever and a new radiodensity on chest X-ray. ACS is a significant cause of hospitalizations and death in children and adults with SCD,” said the study’s lead author, Shaina Willen, MD, of Vanderbilt University Medical Center in Tennessee. ACS is a common complication among SCD patients, affecting roughly 50% at least once in their lifetime. HP1-1, HP1-2 and HP2-2 are the three genetic markers (genotypes) associated with haptoglobin. These genotypes predict how effective an individual’s haptoglobin is at binding to and clearing away excess haemoglobin. The haptoglobin in people with the HP2-2 genotype is not as effective in haemoglobin-binding, and HP22 has been linked to increased cellular (oxidative) damage. The research team hypothesized that patients with the HP2-
2 genotype would be more susceptible to SCD-related complications including ACS, pain, stroke, retinal problems in the eyes, kidney disease and high blood pressure in the arteries of the lungs than patients with HP1-1 and HP1-2 genotypes. The researchers tested 58 adults with SCD and found that 90% of those with the HP2-2 genotype had two or more SCD-related complications compared with 46.7% and 56.3% of those with the HP1-1 and HP1-2 genotypes, respectively. “Our study has identified an increased risk for the development of sickle cell disease-related complications among adult participants with the HP2-2 genotype,” Willen explained. “We have also found that children with the HP2-2 genotype are at increased risk for the development of pain episodes which is the most common cause of hospitalization in children and adults with SCD. “This finding may identify both adults and children at risk for developing diseaserelated complications. The impact of the HP2-2 genotype on the ability of haptoglobin to scavenge products of haemolysis may provide therapeutic targets to investigate related to the oxidative effect of cellfree haemoglobin and the pathophysiology of complications in SCD.” Brain astrocytes linked to Alzheimer’s disease Astrocytes, the supporting cells of the brain, could play a significant role in the pathogenesis of Alzheimer’s disease (AD), according to a new study from the University of Eastern Finland. This is the first time researchers discovered a direct association between astrocytes and AD. Published in Stem Cell Reports, the study investigated the brain cell function of familial AD patients by using stem cell technologies. Alzheimer’s disease is the most common dementia type, with no treatment to slow down the progression of the disease currently available. The mechanisms of AD are poorly understood, and drug therapy has focused on restoring the normal function of neurons and microglia, i.e. cells mediating brain inflammation. The new
study shows that astrocytes, also known as the housekeeping cells of the brain, promote the decline of neuron function in AD. The findings suggest that at least some familial forms of AD are strongly associated with irregular astrocyte function, which promotes brain inflammation and weakens neurons’ energy production and signalling. Astrocytes are important brain cells, as they support neurons in many different ways. Astrocytes are responsible, for example, for the energy production of the brain, ion and pH balance, and they regulate synapse formation, the connections between neurons. Recent evidence suggests that human astrocytes are very different from their rodent counterparts and thus, it would be essential to use human cells to study human diseases. However, the availability of human astrocytes for research has been very limited. The study used the induced pluripotent stem cell technology, which enables the generation of pluripotent stem cells from human skin fibroblasts. These induced stem cells can then be further differentiated to brain cells, e.g. neurons and astrocytes, with the same genetic background as the donor had. The study compared astrocytes from familial AD patients carrying a mutation in the presenilin 1 gene to astrocytes from healthy donors, and the effects of these cells on healthy neurons were also analysed. The researchers found that astrocytes in patients with Alzheimer’s disease produced significantly more beta-amyloid than astrocytes in persons without AD. Beta-amyloid is a toxic protein that is known to accumulate in the brains of AD patients. In addition, AD astrocytes secreted more cytokines, which are thought to mediate inflammation. AD astrocytes also showed alterations in their energy metabolism which likely led to increased production of reactive oxygen species and reduced production of lactate, an important energy substrate for neurons. Finally, when astrocytes were co-cultured with healthy neurons, AD astrocytes caused significant changes on the signalling activity of neu-
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