A team of cardiovascular researchers from the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai, Sanford-Burnham Medical Research Institute, and University of California, San Diego have identified a small, but powerful, new player in the onset and progression of heart failure. Their findings also show how they successfully blocked the newly discovered culprit to halt the debilitating and chronic life-threatening condition in its tracks.
In the study, investigators identified a tiny piece of RNA called miR-25 that blocks a gene known as SERCA2a, which regulates the flow of calcium within heart muscle cells. Decreased SERCA2a activity is one of the main causes of poor contraction of the heart and enlargement of heart muscle cells leading to heart failure. Using a functional screening system developed by researchers at Sanford-Burnham, the research team discovered miR-25 acts pathologically in patients suffering from heart failure, delaying proper calcium uptake in heart muscle cells.
‘Before the availability of high-throughput functional screening, our chance of teasing apart complex biological processes involved in disease progression like heart failure was like finding a needle in a haystack,’ says study co-senior author Mark Mercola, PhD, professor in the Development, Aging, and Regeneration Program at Sanford-Burnham and professor of Bioengineering at UC San Diego Jacobs School of Engineering. ‘The results of this study validate our approach to identifying microRNAs as potential therapeutic targets with significant clinical value.’
Dr. Mercola’s laboratory has pioneered the use of robotic high-throughput methods of drug discovery to identify new targets for heart failure. According to co-lead study authors Christine Wahlquist and Agustin Rojas Muñoz, PhD, developers of the approach and researchers in Mercola’s lab at Sanford-Burnham, they used high-throughput robotics to sift through the entire genome for microRNAs involved in heart muscle dysfunction.
Subsequently, the researchers at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai found that injecting a small piece of RNA to inhibit the effects of miR-25 dramatically halted heart failure progression in mice. In addition, it also improved their cardiac function and survival.
‘In this study, we have not only identified one of the key cellular processes leading to heart failure, but have also demonstrated the therapeutic potential of blocking this process,’ says co-lead study author Dongtak Jeong, PhD, a post-doctoral fellow at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai in the laboratory of the study’s co-senior author Roger J. Hajjar, MD.
Nearly 6 million Americans suffer from heart failure, which is when the heart becomes weak and cannot pump enough blood and oxygen throughout the body. Heart failure is a leading cause of hospitalisation in the elderly. Often, a variety of medications are used to provide heart failure patients temporary relief of their debilitating symptoms. However, these medications do not improve cardiac function or halt the progression of the disease. Mount Sinai Health System

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Finnish healthcare company Biohit Oyj and Randox Laboratories have signed a licensing agreement which gives Randox the worldwide licensing rights for GastroPanel developed by Biohit. GastroPanel is a simple, non-invasive blood test for the diagnosis and screening of gastric disorders. GastroPanel test reliably detects H. pylori infection and damage or dysfunction of the stomach mucosa (atrophic gastritis), leading to acid-free stomach. According to the latest studies, non-acid stomach is a remarkable risk factor for gastric and esophageal cancer. GastroPanel is a non-invasive blood test that reliably identifies both healthy and unhealthy stomachs as well as helps to prioritize patients for further examinations. According to Biohit Oyj CEO Semi Korpela, “The combination of GastroPanel reagents with Randox analysers opens up new distribution possibilities for both companies”. Dr. Peter FitzGerald CBE, Managing Director of Randox, comments “The addition of the Biohit GastroPanel will add significantly to the range of diagnostic products we offer. Our ability to deliver these biomarkers to healthcare providers using our Biochip Array systems will enable diagnosis of gastric disorders in patients with dyspepsia ensuring appropriate further investigation and treatment and contribute to a reduction in healthcare costs. The GastroPanel will be offered in Randox analysers used in hospitals and reference laboratories through our global distribution network in 145 countries.”

The Quo-Lab HbA1c point-of-care analyser has successfully achieved International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) certification. The IFCC maintains the JCTLM (Joint Committee for Traceability in Laboratory Medicine) endorsed reference measurement procedure for HbA1c, accepted worldwide as the analytical control for traceability of HbA1c measurement. To participate in the programme manufacturers are required to register and report the results of 24 samples (two per month) from across the measurement range. The samples are supplied by an IFCC Reference Laboratory. Together with the existing NGSP certification achieved from 2012, the IFCC award demonstrates that Quo-Lab meets all of the demanding standards set by independent certifying bodies.  

Doctors commonly use magnetic resonance imaging (MRI) to diagnose tumours, damage from stroke, and many other medical conditions. Neuroscientists also rely on it as a research tool for identifying parts of the brain that carry out different cognitive functions.

Now, a team of biological engineers at MIT is trying to adapt MRI to a much smaller scale, allowing researchers to visualise gene activity inside the brains of living animals. Tracking these genes with MRI would enable scientists to learn more about how the genes control processes such as forming memories and learning new skills, says Alan Jasanoff, an MIT associate professor of biological engineering and leader of the research team.

‘The dream of molecular imaging is to provide information about the biology of intact organisms, at the molecule level,’ says Jasanoff, who is also an associate member of MIT’s McGovern Institute for Brain Research. ‘The goal is to not have to chop up the brain, but instead to actually see things that are happening inside.’

To help reach that goal, Jasanoff and colleagues have developed a new way to image a ‘reporter gene’ — an artificial gene that turns on or off to signal events in the body, much like an indicator light on a car’s dashboard. In the new study, the reporter gene encodes an enzyme that interacts with a magnetic contrast agent injected into the brain, making the agent visible with MRI. This approach allows researchers to determine when and where that reporter gene is turned on.
MRI uses magnetic fields and radio waves that interact with protons in the body to produce detailed images of the body’s interior. In brain studies, neuroscientists commonly use functional MRI to measure blood flow, which reveals which parts of the brain are active during a particular task. When scanning other organs, doctors sometimes use magnetic ‘contrast agents’ to boost the visibility of certain tissues.

The new MIT approach includes a contrast agent called a manganese porphyrin and the new reporter gene, which codes for a genetically engineered enzyme that alters the electric charge on the contrast agent. Jasanoff and colleagues designed the contrast agent so that it is soluble in water and readily eliminated from the body, making it difficult to detect by MRI. However, when the engineered enzyme, known as SEAP, slices phosphate molecules from the manganese porphyrin, the contrast agent becomes insoluble and starts to accumulate in brain tissues, allowing it to be seen.

The natural version of SEAP is found in the placenta, but not in other tissues. By injecting a virus carrying the SEAP gene into the brain cells of mice, the researchers were able to incorporate the gene into the cells’ own genome. Brain cells then started producing the SEAP protein, which is secreted from the cells and can be anchored to their outer surfaces. That’s important, Jasanoff says, because it means that the contrast agent doesn’t have to penetrate the cells to interact with the enzyme.

Researchers can then find out where SEAP is active by injecting the MRI contrast agent, which spreads throughout the brain but accumulates only near cells producing the SEAP protein.
In this study, which was designed to test this general approach, the detection system revealed only whether the SEAP gene had been successfully incorporated into brain cells. However, in future studies, the researchers intend to engineer the SEAP gene so it is only active when a particular gene of interest is turned on.

Jasanoff first plans to link the SEAP gene with so-called ‘early immediate genes,’ which are necessary for brain plasticity — the weakening and strengthening of connections between neurons, which is essential to learning and memory.

‘As people who are interested in brain function, the top questions we want to address are about how brain function changes patterns of gene expression in the brain,’ Jasanoff says. ‘We also imagine a future where we might turn the reporter enzyme on and off when it binds to neurotransmitters, so we can detect changes in neurotransmitter levels as well.’ MIT