Tag: newsworthy

Categories : Respiratory DiseasesTags :

Small RNA Molecule Holds COPD Treatment Potential

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Photo by Robina Weermeijer on Unsplash

Researchers have identified a small RNA molecule called microRNA-21 as a therapeutic target and its inhibition as a potential treatment for chronic obstructive pulmonary disease (COPD). An inflammatory lung disease that makes it hard to breathe, COPD is the third most common cause of death in the world. It is often caused by smoking tobacco products or inhaling air pollution.

In the pre-clinical study which was published in Science Translational Medicine, the researchers found elevated levels of microRNA-21 in mouse models of COPD. MicroRNA-21 inhibitor (antagomir-21) as a therapeutic treatment reduced inflammation and improved lung capacity and function in these models.

The researchers said antagomir-21 both reduced microRNA-21 expression and also suppressed the influx of inflammatory cells – macrophages, neutrophils and lymphocytes – into the airways and lungs. Lung cytokine production, that amplifies inflammatory responses, was also inhibited through use of antagomir-21.

The paper’s senior author, Professor Phil Hansbro, said that their findings offered up a completely new understanding of COPD.

“MicroRNA-21 is a common molecule that is expressed in most cells in the human body and regulates many critical biological processes. Our findings demonstrate, however, that microRNA-21 levels increase when it comes to COPD,” said Professor Hansbro.

“We believe that the development of new drugs that inhibit microRNA-21 may offer up an entirely new therapeutic approach when it comes to COPD treatment.”

Professor Hansbro said that the findings may address the limited effectiveness that current therapies have in controlling COPD or halting its progression.

“The development of effective COPD treatments has been hampered by a lack of understanding of the disease’s underlying mechanisms. Our data defines microRNA-21 as a novel therapeutic target and its inhibitors as a potential new treatment for this major, currently intractable lung disease.”

Source: News-Medical.Net

Categories : CancerTags : 1 Comment

A New Understanding of How Moles Turn into Melanoma

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Melanoma cells. Source: National Cancer Institute.

Moles and melanomas are both skin tumours that come from melanocytes. Moles are usually harmless, while melanomas are cancerous and often deadly without treatment. A study published in eLife Magazine explains how common moles and melanomas form and why sometimes moles turn into melanoma.

Melanocytes produce melanin that protects the skin against UV radiation. Specific changes to the DNA sequence of melanocytes, called BRAF gene mutations, are found in over 75% of moles. The same change is also found in 50% of melanomas and is common in lung, colon and other cancers. It was thought that when melanocytes only have the BRAFV600E mutation the cell stops dividing, resulting in a mole. When melanocytes have other mutations with BRAFV600E, they divide uncontrollably, turning into melanoma. This model is called ‘oncogene-induced senescence’.

“A number of studies have challenged this model in recent years,” said Robert Judson-Torres, PhD, Huntsman Cancer Institute (HCI) researcher and University of Utah (U of U) assistant professor. “These studies have provided excellent data to suggest that the oncogene-induced senescence model does not explain mole formation but what they have all lacked is an alternative explanation – which has remained elusive.”

The study team took moles and melanomas donated by patients and used transcriptomic profiling and digital holographic cytometry. Transcriptomic profiling lets researchers determine molecular differences between moles and melanomas. Digital holographic cytometry helps researchers track changes in human cells.

“We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes become melanomas,” said Prof Judson-Torres.

The study shows that additional mutations for melanocytes to turn into melanoma are not needed, but environmental signalling can be a trigger for the cells. Melanocytes express genes in different environments, instructing them to either divide uncontrollably or stop dividing altogether.

“Origins of melanoma being dependent on environmental signals gives a new outlook in prevention and treatment,” said Prof Judson-Torres. “It also plays a role in trying to combat melanoma by preventing and targeting genetic mutations. We might also be able to combat melanoma by changing the environment.”

These findings create a foundation for researching potential melanoma biomarkers, allowing doctors to spot cancerous changes in the blood sooner. The researchers are also keen to use these data to better understand potential topical agents to reduce risk melanoma risk, delay development, or stop recurrence, and to detect melanoma early.

Source: Huntsman Cancer Institute

Categories : ExerciseTags :

Exercise Really is a Natural High

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Photo by Brian Erickson on Unsplash

Researchers have found that exercise increases endocannabinoids, helping reduce inflammation and could potentially help treat certain conditions such as arthritis, cancer and heart disease.

A new study, published in Gut Microbes, found that exercise intervention in people with arthritis, in addition to reducing pain, also lowered the levels of inflammatory cytokines. It also increased levels of endocannabinoids, cannabis-like substances produced by the body. Interestingly, exercise caused these changes through an unusual mechanism: altering the gut microbes.

Exercise is known to reduce chronic inflammation, which is linked to a number of diseases including cancer, arthritis and heart disease. However, little is known as to exactly how exercise reduces inflammation.

Researchers tested 78 people with arthritis. Thirty-eight of them carried out 15 minutes of muscle strengthening exercises every day for six weeks, and 40 did nothing.

At the end of the study, those in the exercise intervention group had not only reduced their pain, but they also had more gut microbes that produce anti-inflammatory substances, lower levels of cytokines and higher levels of endocannabinoids.

The increase in endocannabinoids was strongly linked to changes in the gut microbes and anti-inflammatory substances produced by gut microbes called SCFAS. At least a third of the anti-inflammatory effects of the gut microbiome was attributable to the increase in endocannabinoids.

“Our study clearly shows that exercise increases the body’s own cannabis-type substances. Which can have a positive impact on many conditions. As interest in cannabidiol oil and other supplements increases, it is important to know that simple lifestyle interventions like exercise can modulate endocannabinoids,” said Doctor Amrita Vijay, a Research Fellow in the School of Medicine and first author of the paper

Source: University of Nottingham

Categories : Obstetrics & GynaecologyTags :

Tranexamic Acid Cuts Blood Loss in Myomectomies

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Photo by Piron Guillaume on Unsplash

The use of tranexamic acid (TXA) reduced blood loss during myomectomies in women with large uterine fibroids, a retrospective cohort study has found.

Patients who underwent a myomectomy to remove uterine fibroids with a total weight greater than 173 g had lower estimated blood loss after receiving TXA compared with those who did not (205.6 mL vs 405.4 mL), reported Rachel Cullifer, MD, at the virtual American Association of Gynecologic Laparoscopists (AAGL) annual meeting. Furthermore, patients whose largest fibroid was greater than 73 mm had lower levels of blood loss with TXA (229.2 mL vs 408.3 mL).

“TXA is a highly safe hemostatic agent that gynecologic surgeons can utilize during myomectomies,” Cullifer said. “There is a role for TXA in myomectomies performed with a minimally invasive approach,” she added, noting that the treatment should be strongly considered for patients suspected of having a large fibroid burden.

When looking at all myomectomies not stratified by fibroid characteristics, there was not no significant difference in estimated blood loss between patients who received TXA and those who did not (184 mL vs 266 mL). Fibroids are the primary indication for hysterectomy in the US, Dr Cullifer noted, but myomectomy provides a safe alternative for those who want to preserve their fertility.

“Despite advances in laparoscopic techniques, blood loss and blood transfusions still remain higher in myomectomies when compared with hysterectomy,” Dr Cullifer pointed out, adding that elevated plasmin levels during surgery can result in prolonged bleeding. TXA lowers plasmin function and productivity, reducing blood loss, she stated.

Dr Cullifer and colleagues focused on fibroid characteristics to find out which patients might benefit most from TXA.

The researchers analysed patients who had a myomectomy from 2015 to 2020, compared myomectomy cases treated with TXA versus those that were not, and measured estimated blood loss, blood transfusion administration, and operative time. Of the 71 patients who had a myomectomy, 26 received TXA and 45 did not. The average estimated blood loss was 236 mL, and almost all patients underwent minimally invasive procedures, with 53% undergoing laparoscopic surgery and 40% undergoing robot-assisted procedures.

Save for age, all demographic characteristics were similar between the two groups. Patients who received TXA were an average of two and a half years younger than those who did not. Fibroid characteristics were also similar between the two groups. Additionally, adverse events were similar between the two groups. There was one case of thromboembolism in the cohort who did not receive TXA.

Source: MedPage Today

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

An End to The ‘Therapeutic Drought’ in Atopic Dermatitis

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Source: NCI

The end of a longstanding “therapeutic drought” in atopic dermatitis (AD) is in sight as improved understanding of the pathogenesis and pathophysiology has stoked development of multiple drug candidates, according to a leading expert in the field.

“We did have treatments like cyclosporine, that are not specific as we know, and they are not treatments we can give our patients for long-term disease control,” said Emma Guttman-Yassky, MD, of the Icahn School of Medicine at Mount Sinai, during the Inflammatory Skin Diseases Summit.

She said that overcoming this drought was not easy, mostly because “we didn’t have enough understanding of the disease and its pathogenesis, really preventing therapeutic development for patients with atopic dermatitis,” she said.

New AD therapies built on the trail made for psoriasis treatment, starting with basic studies that produced insights into pathogenesis, leading to hypotheses that eventually could be tested in clinical trials, she said. Progress was accompanied by many failures in early stages of therapeutic development in psoriasis.

“One failure that I remember very vividly from psoriasis was the failure of interferon-gamma targeting,” Dr Guttman-Yassky recounted. “In atopic dermatitis, we also had our share of this type of failure, but these failures really helped shape therapeutic directions for all the diseases we are now targeting, including atopic dermatitis.”

This rocky development has led to recognition that AD is a complex disease involving multiple pathogenetic components, including barrier dysfunction, immune abnormalities, disruption of the dermal microbiome, and the peripheral and central nervous systems that play a central role in itch and other disease manifestations.

“Of all the major components involved in AD pathogenesis, immune targeting is the most tractable,” said Dr Guttman-Yassky. “Immune abnormalities are the most important because they perpetuate the disease phenotype of atopic dermatitis, from the nonlesional skin to acute disease and chronic lesions.”

In contrast to psoriasis, AD is a more heterogeneous disease with multiple clinical phenotypes that correlate with differences in immune polarisation and barrier dysfunction. All of the phenotypes exhibit activation of the type 2 inflammatory pathway as a common feature. Across the spectrum of clinical phenotypes, additional cytokine targeting may be required to achieve disease control.

Understanding that AD arises from systemic inflammation has also helped therapy development. Several studies have suggested that, compared to psoriasis, AD is associated with higher levels of immune activation. Blood samples of patients with AD have shown increased levels of activated T cells, circulatory cytokines, and cardiovascular markers.
The accumulation of new insights into AD pathogenesis added no fewer than a dozen viable therapeutic candidates to the pipeline. Dupilumab (Dupixent) led the way in providing the proof of principle that Th2-specific targeting reverses key pathogenetic factors that drive the disease process in AD.

Dr Guttman-Yassky pointed out how targeting Th2 inflammation with dupilumab led to reversal of barrier defects and lichenisation typical of AD as early as 4 weeks, and that by 16 weeks lesional and nonlesional skin looked similar. Furthermore, markers of epidermal hyperplasia and proliferation were “completely wiped out.”

Dr Guttman-Yassky highlighted several key classes of AD drug candidates with potential to build on the success of targeting inflammation: Interleukin-13 inhibition, OX40 inhibition and JAK/STAT inhibition, which showed promising results.

“With these types of response rates, our treatment goals for our patients are evolving,” said Dr Guttman-Yassky.

Source: MedPage Today

Categories : COVIDTags :

Scientist Identify the Gene Responsible for Doubling Severe COVID Risk

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Image source: Pixabay

Scientists at Oxford University have identified the gene responsible for doubling the risk of respiratory failure from COVID. Some 60% of people of South Asian descent carry the high-risk genetic signal, partly explaining the impact of COVID in the Indian subcontinent and the excess deaths seen in some UK communities.

Prior research already identified a stretch of DNA on chromosome 3 which doubled the COVID mortality risk of adults under 65. However, scientists did not know how this genetic signal worked to increase the risk, nor the exact genetic change that was responsible.

In a study published in Nature Genetics, an Oxford University team used cutting edge technology to work out which gene was causing the effect, and how it was doing so.

Study co-lead Jim Hughes, Professor of Gene Regulation, said: “The reason this has proved so difficult to work out, is that the previously identified genetic signal affects the ‘dark matter’ of the genome. We found that the increased risk is not because of a difference in gene coding for a protein, but because of a difference in the DNA that makes a switch to turn a gene on. It’s much harder to detect the gene which is affected by this kind of indirect switch effect.”

The team trained an artificial intelligence algorithm to analyse huge quantities of genetic data from hundreds of types of cells from all parts of the body, to show that the genetic signal is likely to affect cells in the lung. Then the researchers used a newly developed precision technique to zero in on the DNA at the genetic signal. This examines the way that the billions of DNA letters fold up to fit inside a cell to locate the specific gene that was being controlled by the sequence that increases severe COVID risk.

Dr Damien Downes, who led laboratory work, said: “Surprisingly, as several other genes were suspected, the data showed that a relatively unstudied gene called LZTFL1 causes the effect.”

The researchers found that the higher risk version of the gene probably prevents the cells lining airways and the lungs from responding to the virus properly. But importantly it doesn’t affect the immune system, so the researchers expect people carrying this version of the gene to respond normally to vaccines.

The researchers are also hopeful that drugs and other therapies could target the pathway preventing the lung lining from transforming to less specialised cells, raising the possibility of new treatments customised for those most likely to develop severe symptoms.

Study co-lead Professor James Davies, Associate Professor of Genomics at Oxford University, said: “The genetic factor we have found explains why some people get very seriously ill after coronavirus infection. It shows that the way in which the lung responds to the infection is critical. This is important because most treatments have focussed on changing the way in which the immune system reacts to the virus.”

About 60% of people with South Asian ancestry carried this higher-risk version of the gene compared to 15% of those with European ancestry – explaining in part the higher death rates and hospitalisations in the former group. The study also found that 2% of people with Afro-Caribbean ancestry carried the higher risk genotype, meaning that this genetic factor does not completely explain the higher death rates reported for black and minority ethnic communities.

Prof Davies explained: “The higher risk DNA code is found more commonly in some black and minority ethnic communities but not in others. Socioeconomic factors are also likely to be important in explaining why some communities have been particularly badly affected by the COVID pandemic.

“Although we cannot change our genetics, our results show that the people with the higher risk gene are likely to particularly benefit from vaccination. Since the genetic signal affects the lung rather than the immune system, it means that the increased risk should be cancelled out by the vaccine.”

Source: Oxford University

Categories : Cardiovascular DiseaseTags :

Better Outcomes with Earlier Adrenaline Treatment in Cardiac Arrest

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Source: Mat Napo on Unsplash

Earlier adrenaline treatment during a cardiac arrest is linked to better recovery compared to later treatment, according to preliminary research to be presented at the American Heart Association’s Resuscitation Science Symposium (ReSS) 2021.

“Our study’s findings should guide emergency medical services professionals towards earlier administration of epinephrine [adrenaline] during out-of-hospital cardiac arrest management,” said lead study author Shengyuan Luo, MD, MHS, an internal medicine resident physician at Rush University Medical Center in Chicago.

Previous research found that only about 1 in 5 people survive a cardiac arrest outside of the hospital and those who do survive often have long-term impairment in the ability to perform daily living tasks.

During a cardiac arrest, immediate CPR (cardiopulmonary resuscitation) is critical. For some types of cardiac arrest, an AED (automated external defibrillator) also is used to deliver an electric shock through the chest to the heart to restore a heartbeat. For these ‘shockable’ cardiac arrests, adrenalineis injected to help restore blood flow. Previous research indicated that adrenaline should be given after three unsuccessful electric shocks with an AED, however, it was unclear whether it should be given even earlier – such as after the first electric shock.

To compare the effects of earlier versus later administration of adrenaline, the researchers examined medical records to compare epinephrine timing to patient recovery. Study subjects included 6416 multi-ethnic adults across North America who had an out of hospital cardiac arrest with shockable initial rhythm from 2011-2015. They were an average age of 64 years, and most were men.

Overall, adrenaline administration within four minutes after the first shock from an AED was associated with greater chances of recovery, while administration after four minutes was associated with reduced chances. Specifically, people who received adrenaline after four minutes were nearly half as likely to have heartbeat and blood flow restored before hospital admittance and half as likely to survive to hospital discharge or be able to perform daily tasks, as measured by a standard test, at discharge. Additionally, the risks of later adrenaline treatment rose with each minute of delayed treatment.

“It is crucial that whenever a cardiac arrest event is suspected, the emergency medical system be notified and activated immediately, so that people with cardiac arrest receive timely, life-saving medical care,” Dr Luo said.

These findings support the latest American Heart Association CPR and Emergency Cardiovascular Care Guidelines, which were released in October 2020. The guidelines indicate adrenaline should be administered as early as possible to maximise good resuscitation outcome chances. The guideline recommendation was based on previous observational data that suggest better outcomes when adrenaline is given sooner.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

Firefighters’ Blood Pressure Soars in an Emergency

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Source: Pixabay CC0

When the emergency alarm sounds, blood pressure (BP) among firefighters often soars, according to preliminary research presented at the American Heart Association’s Scientific Sessions 2021.

“All emergency and first responders should be aware of their health. They should know what their typical blood pressure level is and be aware of how it fluctuates. Most important, if they have high blood pressure, they should make sure it is well-controlled,” said senio author Deborah Feairheller, PhD.

The study recruited 37 male and 4 female volunteer and municipal firefighters who wore ambulatory BP monitors during an on-call work shift lasting at least 12 consecutive hours. In addition to the automatic BP readings from the monitor, study participants were instructed to prompt the monitor to take a BP reading whenever a pager or emergency call sounded and whenever they felt they entered a stressful situation. Participants also logged activities and call types for each measurement. The firefighters’ average age was 41.2 years. Average body mass index (BMI) of all participants was 30.3, with BMI ≥ 25 defined as overweight, while BMI ≥ 30 is defined as obesity. The firefighters all had high blood pressure, defined as systolic BP as 130 mm Hg or higher, or a diastolic BP of 80 mm Hg or higher, as defined by the American Heart Association’s most recent guideline.

The findings were that:

  • Average BP and heart rate (HR) were 131/79.3 mmHg and 75.7 beats per minute (bpm) respectively.
  • Compared with the reading immediately preceding the call, systolic BPsurged an average of 19.2 mm Hg with fire calls and 18.7 mm Hg with medical calls.
  • Meanwhile, diastolic BP surged 10.5 mm Hg with fire calls and 16.5 mm Hg with medical calls.
  • Compared with the average BP during the entire 12-hour shift, systolic BP was 9% higher during fire calls, and diastolic BP was 9% higher during medical calls.
  • Average HR also increased during both types of calls: 10bpm with fire calls, and 15bpm for medical calls.
  • There were no significant differences in BP, HR or BP surge levels when comparing responses among fire calls, medical calls, riding an emergency vehicle or false alarms.

Surprising findings
“The public knows the value that emergency responders provide to communities. We hope to increase awareness that many firefighters have hypertension and that their blood pressure can increase to very dangerous levels when responding to emergency calls,” said Dr Feairheller.

“The current data show that almost 75% of firefighters have hypertension, and less than 25% have their blood pressure under control. I hope that our research can help identify occupational factors that affect blood pressure and increase awareness among this population,” Dr Feairheller added.

They were also surprised at the findings on diastolic BP increases. “We anticipated systolic blood pressure surges because that reading is usually more responsive to stimuli; however, the extent of the diastolic blood pressure surge was unexpected,” said Dr Feairheller.

The investigators are currently exploring whether diet and exercise regimens could help to lower the BP surge that firefighters experience during emergency calls.

Source: EurekAlert!