Tag: genetics

Categories : CancerTags :

The Effect of Hypoxia on Cancer Cells is a Matter of Timing

On By ModernMedia

A new study from the University of Colorado School of Medicine shows that the effect of hypoxia on cancer cells varies in the short term versus the long term, opening new possibilities for cancer treatment.

How cancer cells adapt to hypoxia, where insufficient oxygen reaches cells, is a key aspect of cancer biology.

“Most tumours cannot grow unless they figure out a way to induce formation of new blood vessels to supply them with oxygen and other nutrients,” explained Matthew Galbraith, PhD. “So, what happens inside of solid tumours is they undergo intermittent periods of low oxygen between rounds of new blood vessel formation.”

Previous research focussed on hypoxia in the long term, characterising it as oncogenic, or cancer promoting. However some studies showed that hypoxia-sensing factors, known as hypoxia inducible factors, or HIFs, can in some situations suppress tumour growth. To solve this, senior researcher Joaquin Espinosa, PhD and colleagues studied the immediate acute response to hypoxia.

“We employed a cutting-edge genomics technology that nobody had employed in this field before that allowed us to see what happens to cancer cells within minutes of depriving them of oxygen,” Dr Espinosa said.

Employing this technology, they identified hundreds of hypoxia-inducible genes activated shortly upon oxygen deprivation. Using computational biology approaches on large, publicly available datasets, they inferred the function of these genes on hundreds of lab-grown cancer cell lines and hundreds of tumour samples from cancer patients.

They found that when a cell is hypoxic, it reacts by ceasing growth to preserve its existing nutrients and oxygen. Thus, hypoxia causes a tumour-suppressive reaction at this point, mostly by preventing protein synthesis. Only after prolonged periods of hypoxia do cells metastasise and spread out in search of oxygen.

“There’s been a lot of debate about whether these hypoxia-inducible factors promote tumour growth or prevent tumour growth,” Dr Espinosa said. “The conclusion we came to is that everyone was right to a degree. Hypoxia-inducible factors can suppress tumour growth by preventing protein synthesis early on, but they can also advance tumour growth at later stages by promoting the ability of cancer cells to invade neighboring tissues. It depends on when you’re looking at it.”

The tumour suppression and promotion mechanisms elicited by HIFs can be exploited as drug targets. Tumour suppression is mediated by inhibition of an enzyme known as mTOR, which in turn can be inhibited by available drugs often used in cancer therapies. “mTOR inhibitors could mimic the tumour suppressive effects of HIFs,” Dr Galbraith explained.

When deprived of oxygen for a longer amount of time, the HIFs switch on a set of enzymes that can degrade the extracellular matrix that holds them in place, allowing the cancer cells to escape the oxygen-deprived tumour. The cancer cells can then enter the bloodstream and invade nearby tissues.

“These results emphasise the importance of developing inhibitors of hypoxia-inducible enzymes that degrade collagen and other components of the extracellular matrix,” Espinosa said.

Dr Espinosa and his team hope that their research will help new cancer treatments to be developed, which also target the cancer at the right times. 

“People have been trying to target the hypoxia-inducible factors with different therapeutics, but this research would suggest that you may want to exercise some caution about when you apply those therapeutics, given that the HIFs can be tumour suppressive in the early stages of hypoxia,” Dr Galbraith said.

“Since the hypoxic response can be tumour suppressive in some contexts and oncogenic in other contexts, it’s not a good idea to issue a blanket statement that we should always try to shut it down,” Dr Espinosa added. “Instead, we should be thinking about what aspect of the hypoxic response to target, and that’s the aspect where hypoxia drives invasion and metastasis.”

Hoping that other researchers would make use of the map his team developed, Dr Espinosa said, “I would say this is a definitive improvement in the mapping of the early events of hypoxia. And the beauty of that is that once you have a good map of the land, a lot of people can use it.”

Source:  Medical Xpress

Journal information: Zdenek Andrysik et al, Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response, Nature Communications (2021). DOI: 10.1038/s41467-021-21687-2

Categories : Genetics Medical Research & TechnologyTags :

New Bioluminescent System Illuminates Biological Processes

On By ModernMedia

Scientists at the Federal University of São Carlos (UFSCar) have developed a new bioluminescent system that can enable greatly improved imaging of biological and pathological processes in organisms.

Luciferases are enzymes that catalyse the oxidation of luciferins present in organisms such as fireflies, which results in bioluminescence in the visible light spectrum. Images of cell cultures and live animal models are made using the luciferin-luciferase system found in fireflies. For example, this can show the structure and activity of tumours, or follow the viral process in cells, helping physicians develop treatments.

“We obtained a novel luciferin-luciferase system that produces far-red light at the wavelength of 650 nanometres and emits the brightest bioluminescence ever reported in this part of the spectrum,” said principal investigator Professor Vadim Viviani, biochemist at UFSCar. “It’s a highly promising result for bioluminescence imaging of biological and pathological processes in mammalian tissues.”

“Red bioluminescence is preferred when imaging biological or pathological processes in mammalian tissues because haemoglobin, myoglobin and melanin absorb little long-wavelength light. Detection is best of all in the far red and near-infrared bands, but bioluminescent systems that naturally emit far red light don’t exist,” Prof Viviani added.

“Some genetically modified forms of luciferase and synthetic analogs of natural luciferins are produced commercially. In conjunction, they produce light at wavelengths as long as 700 nanometers, but the light produced by these artificial systems is generally much weaker and more short-lived than light from natural bioluminescent systems.”

Prof Viviani and collaborators genetically modified luciferase from the Railroad worm Phrixothrix hirtus, the only luciferase that naturally emits red light, and combined with luciferin analogues synthesised by colleagues at the University of Electro-Communications in Tokyo. The resulting luciferin-luciferase generates a much more efficient far-red bioluminescence.

“Our best combination produces far-red at 650 nanometres, three times brighter than natural luciferin and luciferase, and roughly 1000 times brighter than the same luciferase with a commercial analog,” Viviani said.

“Besides the long-wavelength and intense brightness, our combination has better thermal stability and cell membrane penetrability. Above all, it produces more lasting continuous bioluminescence, taking at least an hour to decay and significantly facilitating the real-time imaging of biological and pathological processes.”

Source: News-Medical.Net

Journal information: Viviani, R. V, et al. (2021) A Very Bright Far-Red Bioluminescence Emitting Combination Based on Engineered Railroad Worm Luciferase and 6′-Amino-Analogs for Bioimaging Purposes. International Journal of Molecular Sciences. doi.org/10.3390/ijms22010303.

Categories : Cancer Immune SystemTags :

Insights into How CAR T Cancer Treatment Works

On By ModernMedia

Researchers have uncovered why some patients respond strongly to chimeric antigen receptor T-cell therapy (CAR T), 

CAR T is a new development in cancer therapy, a treatment approved to treat many types of aggressive B cell leukaemias and lymphomas. Moffitt Cancer Center researchers use mathematical modeling to help explain why CAR T cells work in some patients and not in others, with the response instead tapering off and the disease continuing its progression.

CAR T is a type of personalised immunotherapy that uses a patient’s own T cells to target cancer cells. Many patients have strong responses to CAR T; however, some have only a short response and develop disease progression quickly. The procedure involves T cells from a patient being genetically modified to include a specific receptor targeting cancer cells. 

hemotherapy then lowers some of the patient’s existing normal immune cells to help deal with the influx of CAR T cells that are infused back into the patient, where they can get to work and attack the tumour.

“Treatment success critically depends on the ability of the CAR T cells to multiply in the patient, and this is directly dependent upon the effectiveness of lymphodepletion that reduces the normal T cells before CAR T infusion,” explained co-lead author Frederick Locke, MD, Vice Chair, Blood and Marrow Transplant and Cellular Immunotherapy Department, Moffitt.

In their model, the researchers discovered that tumour eradication is effectively random, but can happen with high probability. The researchers showed that differences in the timing and probability of cures are determined largely by variability among patient and disease factors. The model confirmed that cures tends to happen 20 to 80 days before the CAR T cells decline, while disease tends to progress over a wider time range between 200 to 500 days after treatment.

“Our model confirms the hypothesis that sufficient lymphodepletion is an important factor in determining durable response. Improving the adaptation of CAR T cells to expand more and survive longer in vivo could result in increased likelihood and duration of response,” explained lead author Philipp Altrock, PhD, and assistant member of the Integrated Mathematical Oncology Department at Moffitt.

Source: News-Medical.Net

Journal information: Kimmel, G.J., et al. (2021) The roles of T cell competition and stochastic extinction events in chimeric antigen receptor T cell therapy. Proceedings of the Royal Society B: Biological Sciences. doi.org/10.1098/rspb.2021.0229.

Categories : Cardiovascular DiseaseTags :

Genetic Clues to ‘Silent Strokes’ Uncovered

On By ModernMedia

After years of research, scientists have uncovered genetic clues to ‘silent strokes’, a major cause of vascular dementia, opening up new pathways to prevention and treatment.

Lacunar strokes are caused by the weakening of the walls of small blood vessels in the brain that can be only a millimetre in diameter. Such strokes by these can often happen in a stepwise progression, only to be detected when symptoms are noticeable and damage has been done. Few drugs are available to prevent or treat these kinds of strokes.  

Thus far, only one genetic fault has been linked to lacunar strokes. Professor Hugh Markus, BHF-funded researcher and neurologist at the University of Cambridge led a study working with researchers around the world to investigate the genetics behind lacunar strokes. They believe their breakthrough can yield treatments for lacunar stroke and vascular dementia.

Recruiting participants from around the world after they attended hospital and had an MRI or CT brain scan., the researchers scanned and compared the genetic code of 7338 patients who had a lacunar stroke with 254 798 people who had not. They found 12 genetic regions associated with lacunar strokes

The researchers found that these 12 genetic regions are linked to vascular control, and dysfunctions make the blood-brain barrier more permeable to toxins, and messages sent around the brain slow down or fail to arrive completely.

“These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to,” said study leader Prof Hugh Markus. “Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

First author Dr Matthew Traylor, of the study at Queen Mary University of London, said: “Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation and cardiologist, said: “This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35 000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the future.”

Source: Medical Xpress

Journal information: The Lancet Neurology (2021). DOI: 10.1016/S1474-4422(21)00031-4

Categories : COVIDTags :

How The COVID Variant Was Discovered in South Africa

On By ModernMedia

The so-called South African variant was identified by an international team of researchers, including biomedical scientists from the University of California, Riverside. They explain the process behind discovering the variants, why they are so concerning, and what the future holds.

“The new COVID variants are the next new frontier,” said Adam Godzik, a professor of biomedical sciences in the UC Riverside School of Medicine. “Of these, the SA and Brazil strains are most worrying. They have mutations that make them resistant to antibodies we generate with existing vaccines. It is commonly believed we are in a tight race: Unless we vaccinate people quickly and squash the pandemic, new variants would dominate to the point that all our COVID vaccines would be ineffective.”

Prof Godzik and Arghavan Alisoltani-Dehkordi, a postdoctoral researcher who joined his lab two years ago, helped characterise the new SA variant by providing its spike protein structure using computer simulations.  

Dr Alisoltani-Dehkordi, who was a postdoctoral fellow at the University of Cape Town before she joined UCR, mentioned that research teams at the University of KwaZulu-Natal  and UCT discovered the new SARS-CoV-2 variant from samples collected between October 15 and November 25, 2020, in three provinces. By early November, this variant rapidly became the dominant variant in samples from two provinces. The researchers suggested that this may be due to increased transmissibility or immune escape.

“Each SARS-CoV-2 variant has specific mutations defining it,” Dr Alisoltani-Dehkordi said. “Professor Godzik and I used computer modeling to suggest possible structural and functional consequences of spike protein mutations in the SA lineage. Our analysis, confirmed also by several other research groups, shows that some of the mutations potentially result in a higher transmissibility of the virus and a weaker immune response.”

The SA variant has been detected in 40 countries, and is quite likely present in more still.

“This variant is probably spreading in areas where it has not been sequenced and is, therefore, not identifiable,” Prof Godzik said. “In the US, sequencing is still a slow process. In many parts of the country, including Riverside, we have no information whatsoever about variants.”

The SA variant prompted concern among scientists because its mutations allowed it to evade antibody protection, and potentially, vaccines. Indeed, the AstraZeneca vaccine rollout was halted in South Africa due to the low level of protection against this new variant.

“That’s when it received a high level of interest,” Prof Godzik said. “Subsequent research confirmed it is resistant to vaccines and is spreading. South Africa is doing a good job, however, at controlling the variant through quarantining and other measures.”

Common mutational signatures can be seen in each of the newly emerged SARS-CoV-2 variants of concern in the UK, SA, Brazil, and California. But each of these variants also has a unique set of mutations; for example, the SA and Brazil variants have two unique mutations on spike proteins K417N and E484K, respectively. But, as Prof Godzik explains, there is no single “SA variant”, rather a branch on an evolutionary tree. And viruses can acquire mutations and escape at any time.

Prof Godzik thinks COVID will become a permanent feature of our lives. “It takes six months to develop a flu vaccine,” he said. “Models predict the evolution of the flu virus and vaccines are produced before the variants show up. If the predictions are good, the vaccines work. If they miss, a heavy flu season follows. This is how COVID will likely behave. A lot of effort will be invested in predicting what will happen the following year, vaccines would then be updated, and people will need to get a booster shot.”

Source: University of Riverdale, California

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Diphtheria Resurfacing as a Threat As it Evolves Antibiotic Resistance

On By ModernMedia

Diphtheria is resurfacing as a threat worldwide as it evolves antibiotic resistance and could escape vaccine containment, scientists warn.

Diphtheria cases in recent years have doubled what they were in previous decades, to 16 651 cases in 2018. Although babies are vaccinated against it in high-income countries, there is less coverage in middle- and low-income countries.

Diphtheria is mainly caused by Corynebacterium diphtheriae, spread by coughs and sneezes or close contact with the infected. Usually, the bacteria cause acute infections, driven by the diphtheria toxin—the main target of the vaccine. However, non-toxigenic C. diphtheria can also cause disease.

A team of researchers from the UK and India used genomics to map infections, including a subset from India, where more than half of the globally reported cases occurred in 2018.

Analysing the genomes of 61 bacteria isolated from patients and combining these with 441 publicly available genomes, the researchers were then able to understand how they spread. They also used this information to assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation.

The researchers found clusters to genetically-similar bacteria isolated from different continents, most commonly Asia and Europe. This indicates that C. diphtheriae has been travelling with humans as they spread across the planet.

The diphtheria toxin ch is encoded by the tox gene, for which the researchers found 18 different variations, of which several had the potential to change the structure of the toxin.

Professor Gordon Dougan from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) said: “The diphtheria vaccine is designed to neutralise the toxin, so any genetic variants that change the toxin’s structure could have an impact on how effective the vaccine is. While our data doesn’t suggest the currently used vaccine will be ineffective, the fact that we are seeing an ever-increasing diversity of tox variants suggests that the vaccine, and treatments that target the toxin, need to be appraised on a regular basis.”

First author Robert Will, a PhD student at CITIID, said: “The C. diphtheriae genome is complex and incredibly diverse. It’s acquiring resistance to antibiotics that are not even clinically used in the treatment of diphtheria. There must be other factors at play, such as asymptomatic infection and exposure to a plethora of antibiotics meant for treating other diseases.”

Erythromycin and penicillin are commonly recommended to treat early-stage diphtheria, although there are other classes capable of it. Variants resistant to six of these classes in isolates from the 2010s were identified by the team.

Study leader Dr Ankur Mutreja from CITIID, said: “It’s more important than ever that we understand how diphtheria is evolving and spreading. Genome sequencing gives us a powerful tool for observing this in real time, allowing public health agencies to take action before it’s too late.
“We mustn’t take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form.”

Source: Medical Xpress

Journal information: Will, RC et al. Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheria. Nat Comms; 8 Mar 2021; DOI: 10.1038/s41467-021-21870-5

Categories : Gender GeneticsTags :

Health Conditions Driven By Evolution and Genetic Sex Differences

On By ModernMedia

A new study shows that the human genome has been subject to selection pressures favouring different characteristics in females and males, which makes males more susceptible to a variety of health conditions.

Genetic sex differences have long been known to have an impact on health. On balance, while females have certain conditions unique to them (eg, cervical cancer), or are more prone to (eg, multiple sclerosis), males are more prone to certain medical conditions, bringing down their average life expectancy compared to women.

Their research adds to a body of knowledge on genomic influences on health, which can map hereditary traits onto individuals and populations to guide healthcare. Looking at health conditions through the lens of genomics can help clinicians to better understand them and guide development of new treatments.  

“Our cells have memories and they carry the accumulation of all the changes our ancestors have experienced over millions of years,” said Rama Singh, a McMaster biology professor who wrote the paper with his son, Karun Singh, an associate professor of neuropathology at the University of Toronto, and Shiva Singh (no relation), a biology professor at Western University.

The researchers focussed on autism, which is a good example of the way men and women develop medical conditions differently; though they inherit the same sets of genes from the parents, the expression of those genes differs greatly by sex.

Though human behaviour regarding mate selection has changed, those genetic characteristics remain and continue to be expressed in the health and development of modern men.

The male genome has been shaped over millions of years, and favours reproduction in the early years of male maturity to pass on genes, at the expense of genetic well-being in the long term.

Women are less vulnerable to most health conditions, living longer than men because their genomes have evolved to protect against unhealthy traits in the male genome, resulting in better immunity and more longevity.

The same forces shaping human selection also apply to mental health, even though it is complex. Women are more prone to anxiety and depression, while men are more prone to anti-social disorders.

“If women and men were any more different, they would be different species,” joked corresponding author, Prof Karun Singh.

Male-female imbalance is especially pronounced in autism, with being up to four times more likely to have some form of autism, and are also more likely to have severe symptoms. Evolution has resulted in a higher threshold, protecting females from developing the condition.

Although autism is not solely the result of inherited characteristics, it does appear that boys are more likely to develop it as a result of other inhertied characteristics rendering them more vulnerable to environmental, developmental and other factors that give rise to autism.

“One of the reasons I think this is interesting is that it offers a perspective that is not well represented in the medical literature. This is a really good example of the perspective that geneticists and evolutionary biologists can add to health research,” said Prof Karun Singh.

Source: News-Medical.Net

Journal information: Singh, R. S., et al. (2021) Origin of Sex-Biased Mental Disorders: An Evolutionary Perspective. Journal of Molecular Evolution. doi.org/10.1007/s00239-021-09999-9.

Categories : GeneticsTags :

Study Reveals How Thyroid Subtly Regulates Metabolism

On By ModernMedia

Thyroid hormone appears to regulate metabolism by acting as a ‘dimmer switch’ as opposed to an ‘on/off’ switch, as reported by a new study from the University of Pennsylvania.

The thyroid hormone has long been known to be an important controller of the body’s metabolism, as well development, but how exactly this is achieved remains something of a mystery. Part of this problem was that the thyroid hormone worked inside the nucleus, activating some genes and deactivating others. Being able to observe this process has been extremely challenging.

“We were able in this study to show that thyroid hormone doesn’t just turn things on or off, as the canonical model suggests, but instead more subtly shifts the balance between the repression and enhancement of gene activity,” said principal investigator Mitchell Lazar, MD, PhD, at Penn Medicine. “Yet, as people with hypothyroidism know, the lack of thyroid hormone can have profound effects on the body.”

Knowing how thyroid hormone regulates the body’s metabolism would be a great boon for new drug development, especially to tackle obesity. For four decades, scientists have known that thyroid hormone acts on thyroid hormone receptors, but these special proteins exist in small quantities and marking where they are on DNA has proven difficult.
In the new study, the researchers developed a mouse model in which a special tag was added to TRβ, the main thyroid hormone receptor in the liver, which is where important metabolic effects of thyroid hormone occur. With this tag, they marked the thousands of locations on DNA where TRβ binds, both in states when thyroid hormone was present and could bind to TRβ and also when no hormone was present. In this way, the team came up with strong evidence that shows the unexpectedly subtle manner in which thyroid hormone works with TRβ.

When it binds to a DNA site, TRβ will promote or suppress nearby gene activity by forming complexes with other proteins called co-activators and co-repressors. When thyroid hormone is bound to TRβ, it can alter the balance of these co-regulator proteins towards more gene activation at some sites, and more gene repression at others. Prior models of thyroid hormone / TRβ function in which thyroid hormone has a more absolute, switch-like effect on gene activity.

The researchers acknowledged that more work is needed to discover just how genes are activated or repressed at the sites. However, this is a significant advancement towards treatments which can directly influence the body’s metabolism.

Source: Medical Xpress

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Excessive False Positives from SNP Testing in Very Rare Diseases

On By ModernMedia

A widely-used genetic testing technology has a very high rate of false positives for extremely rare genetic diseases, a study has found.

Single nucleotide polymorphism (SNP) chips are DNA microarrays which test genetic variation at hundreds of thousands of specific genome locations. They were initially developed to study common genetic variations, and are excellent tools for tracing ancestry and aso detecting predisposition to common multifactorial diseases such as type 2 diabetes.

Prompted by accounts of women scheduling surgery because of wrongly being informed they had variations in the BRCA1 gene that could lead to very high risks of breast disease, a team from the University of Exeter set out to test the technology. Using data from 50 000 individuals, they found that the majority of rare disease detections were false.

“SNP chips are fantastic at detecting common genetic variants, yet we have to recognise that tests that perform well in one scenario are not necessarily applicable to others,” said senior author Caroline Wright, Professor in Genomic Medicine at the University of Exeter Medical School. “We’ve confirmed that SNP chips are extremely poor at detecting very rare disease-causing genetic variants, often giving false positive results that can have profound clinical impact. These false results had been used to schedule invasive medical procedures that were both unnecessary and unwarranted.”

The team compared data from the SNP chips to data from the UK Biobank which was sequenced with better technology, plus 21 volunteers sharing their consumer genetic data.

They found a false positive rate of 84% for variants that were 1 in 100 000. From the consumer data, 20 of the 21 had at least one false positive for a disease-causing variation.

Co-author Dr Leigh Jackson, Lecturer in Genomic Medicine at the University of Exeter, said the number of such false positives on SNP chips was “shockingly high.”

“To be clear: a very rare, disease-causing variant detected using a SNP chip is more likely to be wrong than right,” said Dr Jackson. “Although some consumer genomics companies perform sequencing to validate important results before releasing them to consumers, most consumers also download their ‘raw’ SNP chip data for secondary analysis, and this raw data still contain these incorrect results. The implications of our findings are very simple: SNP chips perform poorly for detecting very rare genetic variants and the results should never be used to guide a patient’s medical care, unless they have been validated.”

Source: Medical Xpress

Journal information: BMJ (2021). www.bmj.com/content/372/bmj.n214

Categories : Genetics Injury & TraumaTags :

Plasma microRNAs as Biomarkers for Mild Brain Injury

On By ModernMedia

Plasma microRNA could serve as biomarkers for the detection and diagnosis of mild traumatic brain injury, a recent study from the University of Eastern Finland (UEF) has found.

Mild traumatic brain injury is extremely difficult to detect as it is almost invisible to most imaging techniques, and visible signs in daily life may be masked by compensation for increased task difficulty.

Blood biomarkers can satisfy the demand for timely, accurate, easily accessible and affordable tests for mild traumatic brain injury. They are minimally invasive and can provide molecular information about the injury on an ongoing basis.

MicroRNAs (miRNAs) are non-coding sections of RNA that play a key role in gene expression. The researchers sequenced DNA in blood plasma taken from animal models subjected to mild and severe traumatic brain injury. They selected the miRNAs which showed the greatest potential for use as biomarkers for further analysis with polymerase chain reaction (PCR). They wanted biomarkers that were both sensitive and specific to traumatic brain injury in an animal model.

Dr Noora Puhakka, A. Virtanen Institute for Molecular Sciences, UEF, said, “We have been developing a suitable analysis and measurement method especially for miRNAs that can be found in small amounts in plasma, and this method is based on digital droplet PCR.

“Humans and animals share many identical miRNAs, and this makes them excellent candidates for translational studies, where results achieved in animal models are sought to be applied in humans. However, it has proven challenging to reproduce results from different studies and different sets of data. This is why assessing the quality of measurement methods, and reproducibility, is an extremely important part of biomarker research.”
The study a pair of possible biomarker candidates to diagnose mild traumatic brain injury both in the animal model and in human patients.  

“We found two interesting biomarkers in the animal model, the plasma miRNAs miR-9a-3p and miR-136-3p, which we then decided to analyse in blood samples taken from patients with traumatic brain injury. Elevated levels of these biomarkers allowed us to identify some of the patients who had experienced a mild traumatic brain injury,” Dr Puhakka explained.

“Both of these miRNAs are more abundant in the brain than in other tissues, and their elevated levels in plasma could possibly be due to brain injury and the level of its seriousness. However, further research in larger patient cohorts is still needed.”

Source: News-Medical.Net

Journal information: Gupta, S. D., et al. (2021) Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. International Journal of Molecular Sciences. doi.org/10.3390/ijms22041563.