Month: August 2024

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Unique Genetic Pattern can Predict Severe Side Effects of Melanoma Immunotherapy

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Melanoma Cells. Credit: National Cancer Institute

An activity pattern in certain genes responsible for building proteins known as spleen tyrosine kinases can predict which melanoma patients are likely to have severe side effects from immunotherapy designed to treat the most deadly skin cancer, as shown by a new study published in the journal Clinical Cancer Research.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the latest experiments focused on checkpoint inhibitors, drugs that have in the last decade become a mainstay of treating melanoma. This form of skin cancer kills nearly 10 000 Americans annually.

The drugs work by blocking molecules (checkpoints) that sit on the surface of immune T which the immune system uses to recognise and protect healthy cells. Cancer cells are able to hijack and turn off immune cell surveillance, evading detection. Immunotherapy drugs like nivolumab and ipilimumab are designed to block checkpoints, making cancer cells more “visible” again to T cells.

More than a third of melanoma patients given checkpoint inhibitors develop side effects so severe that they compromise their quality of life and ability to continue therapy. Side effects most often involve some form of inflammation, a sign of an overactive immune response. Patients may experience severe skin rashes, diarrhoea, or hyperthyroidism. More-severe side effects can include liver toxicity, colitis, and rheumatoid arthritis.

In the new study researchers found that even before treatment began in their test subjects, the activity of genes controlling the production of spleen tyrosine kinases predicted 83% of melanoma patients who eventually developed severe side effects from combined immunotherapy with nivolumab and ipilimumab.

Moreover, the researchers found that this heightened gene signature, as evidenced by the production of spleen tyrosine kinases, or the SYK pathway, did not interfere with the effectiveness of therapies in preventing recurrence of melanoma. The impact was connected only to side effects.

“Predictive information of this kind is critically important to oncologists and patients to help guide their immunotherapy decisions, to either minimize these side effects by taking additional precautions or to choose alternative immunotherapies,” said study co-senior investigator Tomas Kirchhoff, PhD.

“Our study results show that increased gene activity in the spleen tyrosine kinase pathway could be the basis of a possible blood test that identifies those melanoma patients most susceptible to having severe side effects from immunotherapy, and well before they start treatment,” said study co-lead investigator Kelsey Monson, PhD. 

For the study, researchers analysed immune system cell samples from 212 men and women with melanoma participating in the CheckMate-915 trial. The trial was designed to test whether combined therapy with nivolumab and ipilimumab worked better than single therapy with nivolumab in preventing postsurgical recurrence of melanoma. All immune cell samples were taken prior to the start of immunotherapy. Both drugs are manufactured by the pharmaceutical company Bristol Myers Squibb, which sponsored the CheckMate-915 trial, and provided the patient specimens and data used in the analysis.

When researchers looked at what genes were more active than others in patients who experienced side effects from their immunotherapy, they found a specific pattern among 24 genes tied to the production of spleen tyrosine kinases. Further statistical analyses showed that increased or decreased activity (transcription) of only five of these genes – CD22, PAG1, CD33, HNRNPU, and FCGR2C – along with patients’ age and the stage severity of their melanoma served as the best predictors of who would experience side effects from immunotherapy.

Study co-senior investigator Jeffrey S. Weber, MD, PhD, says that the SYK pathway has previously been linked to other autoimmune diseases, including lupus, rheumatoid arthritis, and colitis. He also points out that immunotherapy side effects were also most common in areas affected by these autoimmune diseases, including the skin, colon, and liver.

Dr Weber says the team next plans to investigate if an activated SYK pathway is predictive of side effects in patients treated with ipilimumab alone or with other combination immunotherapies.

“If our future research can explain how an activated spleen tyrosine kinase pathway leads to increased risk of side effects from immunotherapy, then it could also potentially help us to design better cancer immunotherapies and potentially other treatments for autoimmune diseases,” said Dr Kirchhoff.

Source: NYU Langone Health / NYU Grossman School of Medicine

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Strong Link Between Haem Iron in Red Meat and Type 2 Diabetes Risk

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Photo by Jose Ignacio Pompe on Unsplash

Higher intake of haem iron, the type found in red meat and other animal products – as opposed to non-haem iron, found mostly in plant-based foods – was associated with a higher risk of developing type 2 diabetes (T2D) in a new study published in Nature Metabolism. While the link between haem iron and T2D has been reported previously, the findings from this study, which was led by Harvard T.H. Chan School of Public Health, more clearly establish and explain the link.

“Compared to prior studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers, and cutting-edge metabolomics,” said lead author Fenglei Wang, research associate in the Department of Nutrition. “This allowed us to achieve a more comprehensive understanding of the association between iron intake and T2D risk, as well as potential metabolic pathways underlying this association.”

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206 615 adults (79% female) enrolled in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study. They examined participants’ intake of various forms of iron – total, haem, non-haem, dietary (from foods), and supplemental (from supplements) – and their T2D status, controlling for other health and lifestyle factors.

The researchers also analysed the biological mechanisms underpinning haem iron’s relationship to T2D among smaller subsets of the participants. They looked at 37 544 participants’ plasma metabolic biomarkers, including those related to insulin levels, blood sugar, blood lipids, inflammation, and two biomarkers of iron metabolism. They then looked at 9024 participants’ metabolomic profiles – plasma levels of small-molecule metabolites.

The study found a significant association between higher haem iron intake and T2D risk. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. In addition, the researchers found that haem iron accounted for more than half of the T2D risk associated with unprocessed red meat and a moderate proportion of the risk for several T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intakes of non-haem iron from diet or supplements and risk of T2D.

The study also found that higher haem iron intake was associated with blood metabolic biomarkers associated with T2D. A higher haem iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload, as well as lower levels of beneficial biomarkers like HDL cholesterol and adiponectin.

The researchers also identified a dozen blood metabolites – including L-valine, L-lysine, uric acid, and several lipid metabolites – that may play a role in the link between haem iron intake and TD2 risk. These metabolites have been previously associated with risk of T2D.

On a population level, the study findings carry important implications for dietary guidelines and public health strategies to reduce rates of diabetes, according to the researchers. In particular, the findings raise concerns about the addition of heme to plant-based meat alternatives to enhance their meaty flavor and appearance. These products are gaining in popularity, but health effects warrant further investigation.

“This study underscores the importance of healthy dietary choices in diabetes prevention,” said corresponding author Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology. “Reducing haem iron intake, particularly from red meat, and adopting a more plant-based diet can be effective strategies in lowering diabetes risk.”

The researchers noted that the study had several limitations, including the potential for incomplete accounting for confounders and measurement errors in the epidemiological data. In addition, the findings – based on a study population that was mostly white – need to be replicated in other racial and ethnic groups.

Source: Harvard T.H. Chan School of Public Health

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Parents’ Eating Behaviour Influences how Their Children Respond to Food

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Photo by Vanessa Loring on Pexels

Young children often display similar eating behaviour as their parents, with a parent’s own eating style influencing how they feed their children, research at Aston University has shown.

The work, published in the journal Appetite, suggests that parents can help to shape healthy eating behaviour in their children both by how they themselves eat, as well as how they feed their children.

A team led by Professor Jacqueline Blissett at Aston University, asked parents to assess their own eating behaviour and looked for associations between those behaviours and those of their children.

The team grouped parents into four eating styles – ‘typical eating’, ‘avid eating’, ‘emotional eating’ and ‘avoidant eating’. Typical eaters, who made up 41.4% of the sample, have no extreme behaviours. Avid eaters (37.3%) have high food approach traits such as eating in response to food cues in the environment and their emotions, rather than hunger signals. Emotional eaters (15.7%) also eat in response to emotion but do not enjoy food as much as avid eaters. Avoidant eaters (5.6%) are extremely selective about food and have a low enjoyment of eating.

The direct links between child and parent behaviour were particularly clear in parents with avid or avoidant eating behaviours, whose children tended to have similar eating behaviour. Parents who had avid or emotional eating styles were more likely to use food to soothe or comfort a child, who then in turn displayed avid or emotional eating traits. Where parents with avid or emotional eating traits provided a balanced and varied range of foods, the child was less likely to display the same behaviour.

The research follows on from previous work by the team, which identified the four main types of eating behaviour in children and linked parental feeding practices to those traits.

Dr Abigail Pickard, the lead researcher on the project, said:

“Parents are a key influence in children’s eating behaviour but equally, parents have the perfect opportunity to encourage a balanced diet and healthy eating from a young age in their children. Therefore, it is important to establish how a parent’s eating style is associated with their children’s eating style and what factors could be modified to encourage healthy relationships with food.”

She and the team will now look at developing an intervention to support parents to use other ways to regulate emotions, model healthy eating, and create a healthy home food environment. This could help to prevent less favourable eating behaviours being passed down the generations from parent to child.

Source: Aston University

Categories : AgeingTags : Leave a comment

Turning off Pro-inflammatory Cytokine IL-11 Extends Healthy Lifespan in Mice

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Credit: MRC LMS, Duke-NUS Medical School

Scientists have discovered that ‘turning off’ the cytokine IL-11 can significantly increase the healthy lifespan of mice by almost 25%.

The scientists, at the Medical Research Council Laboratory of Medical Science (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore, tested the effects of IL-11 by creating mice with the gene for IL-11 (interleukin 11) deleted. This extended the lives of the mice by over 20% on average. The cytokine has for years been misidentified as an anti-inflammatory and anti-fibrotic.

They also treated 75-week-old mice, equivalent to the age of about 55 years in humans, with an injection of an anti-IL-11 antibody, a drug that stops the effects of the IL-11 in the body.

Median lifespan extended

The results, published in Nature, were dramatic, with mice given the anti-IL-11 drug from 75 weeks of age until death having their median lifespan extended by 22.4% in males and 25% in females. The mice lived for an average of 155 weeks, compared with 120 weeks in untreated mice.

The treatment largely reduced deaths from cancer in the animals, as well as reducing the many diseases caused by fibrosis, chronic inflammation and poor metabolism, which are hallmarks of ageing. There were very few side effects observed.

Fewer cancers and free from the usual signs of ageing and frailty

Professor Stuart Cook, who was co-corresponding author, from MRC LMS, Imperial College London and Duke-NUS Medical School in Singapore, said:

These findings are very exciting. The treated mice had fewer cancers, and were free from the usual signs of ageing and frailty, but we also saw reduced muscle wasting and improvement in muscle strength. In other words, the old mice receiving anti-IL11 were healthier.

Previously proposed life-extending drugs and treatments have either had poor side-effect profiles, or don’t work in both sexes, or could extend life, but not healthy life, however this does not appear to be the case for IL-11.

While these findings are only in mice, it raises the tantalising possibility that the drugs could have a similar effect in elderly humans. Anti-IL-11 treatments are currently in human clinical trials for other conditions, potentially providing exciting opportunities to study its effects in ageing humans in the future.

The researchers have been investigating IL-11 for many years and in 2018 they were the first to show that IL-11 is a pro-fibrotic and pro-inflammatory protein, overturning years of incorrect characterisation as anti-fibrotic and anti-inflammatory.

Levels of IL-11 increases with age

Assistant Professor Anissa Widjaja, who was co-corresponding author, from Duke-NUS Medical School, Singapore, said:

This project started back in 2017 when a collaborator of ours sent us some tissue samples for another project. Out of curiosity, I ran some experiments to check for IL-11 levels. From the readings, we could clearly see that the levels of IL-11 increased with age and that’s when we got really excited!

We found these rising levels contribute to negative effects in the body, such as inflammation and preventing organs from healing and regenerating after injury. Although our work was done in mice, we hope that these findings will be highly relevant to human health, given that we have seen similar effects in studies of human cells and tissues.

This research is an important step toward better understanding ageing and we have demonstrated, in mice, a therapy that could potentially extend healthy ageing, by reducing frailty and the physiological manifestations of ageing.

Previously, scientists have posited that IL-11 is an evolutionary hangover in humans, as while it is vital for limb regeneration in some animal species, it is thought to be largely redundant in humans.

IL-11 linked to chronic inflammation and frailty

However, after about the age of 55 in humans, more IL-11 is produced and past research has linked this to chronic inflammation, fibrosis in organs, disorders of metabolism, muscle wasting (sarcopaenia), frailty, and cardiac fibrosis. These conditions are many of the signs we associate with ageing.

When two or more such conditions occur in an individual, it is known as multimorbidity, which encompasses a range of conditions including lung disease, cardiovascular disease, diabetes, vision and hearing decline and a host of other conditions.

Professor Cook said:

The IL-11 gene activity increases in all tissues in the mouse with age. When it gets turned on it causes multimorbidity, which is diseases of ageing and loss of function across the whole body, ranging from eyesight to hearing, from muscle to hair, and from the pump function of the heart to the kidneys.

Multimorbidity among biggest global healthcare challenges

Multimorbidity and frailty are acknowledged to be among the biggest global healthcare challenges of the 21st century, according to many leading health bodies, including the NHS and the World Health Organization.

Currently, no treatment for multimorbidity is available, other than to try to treat the separate multiple underlying causes individually.

The scientists caution that the results in this study were in mice and the safety and effectiveness of these treatments in humans need further establishing in clinical trials before people consider using anti-IL-11 drugs for this purpose.

Source: UK Research & Innovation

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Treating Radiation-induced Skin Injuries with Aspirin Hydrogels

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Photo by National Cancer Institute on Unsplash

Radiation is a powerful tool for treating cancer, but prolonged exposure can damage the skin. Radiation-induced skin injuries are painful and increase a person’s chances of infection and long-term inflammation. Now, researchers in ACS Biomaterials Science & Engineering report an aspirin-containing hydrogel that mimics the nutrient-rich fluid between cells and accelerates healing of skin damaged by radiation in animals. With further development, the new salve could provide effective and rapid wound healing for humans. 

Most people undergoing radiotherapy for cancer will experience radiation-induced skin injury that can include redness, pain, ulcers, necrosis and infection. There are few treatments for these wounds, with the most common methods being debridement and hyperbaric oxygenation. Wound dressings made from hydrogels are gaining popularity because they are easy to apply and provide a wet environment for healing that is similar to the inside of the body. Glycopeptide-based hydrogels are especially promising: In laboratory and animal studies, the nanofibre structures have promoted cellular growth and regulated cell adhesion and migration. A research team led by Jiamin Zhang, Wei Wang, Yumin Zhang and Jianfeng Liu proposed loading aspirin, a common anti-inflammatory drug, into a glycopeptide-based hydrogel to create a multifunctional wound dressing for radiation-induced skin injuries.       

In lab tests with cultured cells, the researchers found that the aspirin-contained hydrogel scavenged reactive oxygen species, repaired DNA double-strand breaks and inhibited inflammation caused by radiation exposure without affecting cellular growth. In mouse models of radiation-induced skin injury, the researchers found that dressing wounds for three weeks with the salve reduced acute injuries and accelerated healing – results that the team says point to its potential as an easy-to-administer, on-demand treatment option for reducing radiation damage and promoting healing in humans.

Source: American Chemical Society

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Starvation and Adhesion Drive Formation of Keratinocyte Patterns in Skin

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Skin cell (keratinocyte) This normal human skin cell was treated with a growth factor that triggered the formation of specialised protein structures that enable the cell to move. We depend on cell movement for such basic functions as wound healing and launching an immune response. Credit: Torsten Wittmann, University of California, San Francisco

Fingerprints are one of the best-recognised examples of pattern formation by epithelial cells. The primary cells in the epithelium are the keratinocytes, and they are known to form patterns at the microscopic and macroscopic levels. While factors affecting this pattern formation have been reported, the exact mechanisms underlying the process are still not fully understood.

A team of researchers, led by Associate Professor Ken Natsuga at the Faculty of Medicine, Hokkaido University, have revealed that cell-cell adhesion governs pattern formation in keratinocytes. Their findings were published in the journal Life Science Alliance.

“In this study, we used an immortalised keratinocyte cell line, called HaCaT, which retains all the properties of normal keratinocytes,” Natsuga explained. “In order to ensure that our findings were accurate, we established single-cell cultures from this cell line.”

The team observed pattern formation in both the original heterogeneous cell line, as well as in single-cell-derived cultures. During culturing, the keratinocytes moved randomly and spontaneously formed high- and low-density regions, leading to pattern formation.

The pattern formation was markedly influenced by starvation. When the culture medium was renewed, patterns were obscured, but reappeared as the nutrients in the culture medium were consumed by the keratinocytes.

The team then examined the gene expression in the keratinocytes, which revealed that cell adhesion proteins and keratinocyte differentiation proteins were upregulated in high-density regions. “As cell adhesion is necessary for the development of high-cell-density regions, we specifically investigated the expression of adherens junction (AJ) molecules such as E-cadherin and actin,” Natsuga elaborated. “We found that these molecules were localised at the intercellular junctions of high-density regions.”

The authors then used a mathematical model to confirm that, under spatially uniform density and stress, strong cell adhesion leads to the formation of density patterns. They were also able to demonstrate that the keratinocyte patterns influenced cell proliferation and differentiation, and that serum starvation influences epidermal stratification (a type of differentiation) in skin cells from mice.

“Our study presents a novel and robust model of cell–cell adhesion-induced patterning (CAIP),” concludes Natsuga. “We have deepened our mechanistic insight into cellular organization and its consequences for cell fate decisions and epithelial stratification.”  The team demonstrated that epithelial cell–cell adhesion is essential and sufficient for patterning. Future work will focus on adding more variables to the model to understand other processes that occur concurrently during development.

Source: Hokkaido University

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An ‘Invisible Mask’ Air Curtain that Kills Viruses, Blocks 99.8% of Aerosols

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Taza Aya’s Worker Wearable Protection device keeps airborne virus particles from reaching a workers mouth and nose with an air curtain. That air is pre-treated to kill any viruses. Image credit: Jeremy Little, Michigan Engineering

An air curtain shooting down from the brim of a hard hat can prevent 99.8% of aerosols from reaching a worker’s face. The technology, created by University of Michigan startup Taza Aya, potentially offers a new protection option for workers in industries where respiratory disease transmission is a concern.

Independent, third-party testing of Taza Aya’s device showed the effectiveness of the air curtain, curved to encircle the face, coming from nozzles at the hat’s brim. But for the air curtain to effectively protect against pathogens in the room, it must first be cleansed of pathogens itself. Previous research by the group of Taza Aya co-founder Herek Clack, U-M associate professor of civil and environmental engineering, showed that their method can remove and kill 99% of airborne viruses in farm and laboratory settings.

“Our air curtain technology is precisely designed to protect wearers from airborne infectious pathogens, using treated air as a barrier in which any pathogens present have been inactivated so that they are no longer able to infect you if you breathe them in,” Clack said. “It’s virtually unheard of – our level of protection against airborne germs, especially when combined with the improved ergonomics it also provides.”

Fire has been used throughout history for sterilisation, and while we might not usually think of it this way, it’s what’s known as a thermal plasma. Nonthermal, or cold, plasmas are made of highly energetic, electrically charged molecules and molecular fragments that achieve a similar effect without the heat. Those ions and molecules stabilize quickly, becoming ordinary air before reaching the curtain nozzles.

Taza Aya’s prototype features a backpack, weighing roughly 10 pounds (4.5kg), that houses the nonthermal plasma module, air handler, electronics and the unit’s battery pack. The handler draws air into the module, where it’s treated before flowing to the air curtain’s nozzle array.

Taza Aya’s progress comes in the wake of the COVID pandemic and in the midst of a summer when the U.S. Centers for Disease Control and Prevention have reported four cases of humans testing positive for bird flu. During the pandemic, agriculture suffered disruptions in meat production due to shortages in labour, which had a direct impact on prices, the availability of some products and the extended supply chain.

In recent months, Taza Aya has conducted user experience testing with workers at Michigan Turkey Producers in Wyoming, Michigan, a processing plant that practices the humane handling of birds. The plant is home to hundreds of workers, many of them coming into direct contact with turkeys during their work day.

To date, paper masks have been the main strategy for protecting employees in such large-scale agriculture productions. But on a noisy production line, where many workers speak English as a second language, masks further reduce the ability of workers to communicate by muffling voices and hiding facial clues.

“During COVID, it was a problem for many plants – the masks were needed, but they prevented good communication with our associates,” said Tina Conklin, Michigan Turkey’s vice president of technical services.

In addition, the effectiveness of masks is reliant on a tight seal over the mouth and noise to ensure proper filtration, which can change minute to minute during a workday. Masks can also fog up safety goggles, and they have to be removed for workers to eat. Taza Aya’s technology avoids all of those problems.

As a researcher at U-M, Clack spent years exploring the use of nonthermal plasma to protect livestock. With the arrival of COVID in early 2020, he quickly pivoted to how the technology might be used for personal protection from airborne pathogens.

In October of that year, Taza Aya was named an awardee in the Invisible Shield QuickFire Challenge – a competition created by Johnson & Johnson Innovation in cooperation with the U.S. Department of Health and Human Services. The program sought to encourage the development of technologies that could protect people from airborne viruses while having a minimal impact on daily life.

“We are pleased with the study results as we embark on this journey,” said Alberto Elli, Taza Aya’s CEO. “This real-world product and user testing experience will help us successfully launch the Worker Wearable in 2025.”

Source: University of Michigan

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Do Dietitians have Weight Bases Towards Themselves and Others?

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Photo by I Yunmai on Unsplash

In a survey-based study, UK dietitians exhibited significant weight stigma, both towards themselves and towards others.

The study in the Journal of Human Nutrition and Dietetics involved an online survey completed in 2022 by 402 registered dietitians aged 20–70 years old. Most respondents reported personally experiencing weight stigma prior to (51%) and after becoming (59.7%) registered dieticians, and nearly a quarter (21.1%) felt that their weight influenced their own ability to perform as a dietitian.

Weight stigma was experienced across the weight spectrum. Participants reported explicit (or conscious) weight bias attitudes, moderate beliefs that obesity is controllable, and implicit (or unconscious) anti-fat bias.

“The study highlights the need to address weight stigma and its implications within the dietetic profession,” the authors wrote.

Source: Wiley

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Controlling Lipid Levels with Less Side Effects Possible with New Drug

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Image Credit: Institute of Transformative Bio-Molecules (ITbM), Nagoya University

Researchers at Nagoya University in Japan have developed a new compound, ZTA-261, that binds to thyroid hormone receptor beta (THRβ). THRβ plays an important role in the regulation of lipid metabolism, which affects lipid levels in the blood. Mice administered the drug showed decreased lipid levels in the liver and blood, with fewer side effects in the liver, heart, and bones compared to existing compounds.  These findings, published in Communications Medicine, suggest that ZTA-261 is an effective treatment for lipid disorders such as dyslipidaemia.

Approximately one in ten people is classified as obese or overweight, often due to abnormalities in lipid metabolism. Abnormal levels of lipids in the blood, known as dyslipidaemia, lead to an increased risk of chest pain, heart attack, and stroke.

There is growing interest in developing treatments for dyslipidaemia that leverage the properties of thyroid hormones. Thyroid hormones increase overall metabolism through binding to two types of receptors: alpha (THRα) and beta (THRβ). The brain, heart, and muscle contain the α-subtype, whereas the liver and pituitary gland primarily express the β-subtype.

Treatments that rely on THR activation face challenges due to the side effects of thyroid hormones. Although THRα regulates cardiovascular functions, excess levels of thyroid hormone lead to adverse effects in nearby organs such as heart enlargement and muscle and bone wasting. On the other hand, activation of THRβ influences lipid metabolism without these severe side effects.

As a result, THRβ has become a desirable target for treating metabolic disorders such as dyslipidaemia. However, common treatments, such as the natural thyroid hormone T3, show almost no selectivity between the α and β receptors, making it difficult to avoid the severe side effects caused by binding to THRα.

To address this problem, a research team, including Masakazu Nambo, Taeko Ohkawa, Ayato Sato, Cathleen Crudden, and Takashi Yoshimura from Nagoya University’s WPI-ITbM, developed ZTA-261, a thyroid hormone derivative drug with a similar structure. To test its efficacy, they compared it with GC-1, another thyroid hormone derivative, and the natural thyroid hormone T3 in a mouse model.

They found that ZTA-261 had almost 100 times higher selectivity for THRβ than THRα. In comparison, GC-1 showed only a 20-fold difference in affinity, showing ZTA-261’s superior selectivity. This was confirmed by the significant increase in heart weight and bone damage indicators in T3-treated mice but not in those treated with ZTA-261.

“Our findings suggest that ZTA-261 is much less toxic than T3 and even less toxic than GC-1, which is known as a THRβ-selective compound,” Ohkawa said. “I find it amazing that the difference in THR beta-selectivity between ZTA-261 and GC-1 – 100 times selectivity versus 20 times selectivity – truly has this big an impact on heart and bone toxicity.”

As many drugs have been discontinued in preclinical trials because of their toxicity in the liver, the researchers checked for potential liver toxicity by measuring alanine aminotransferase (ALT) levels in the blood. Their findings confirmed the safety of the drug, finding no significant differences in ALT levels between mice treated with ZTA-261 and those treated with saline. Although these results are promising, more studies, including human trials, will be necessary before considering ZTA-261 for clinical use. However, this breakthrough represents a significant step forward in the development of safer treatments for lipid disorders.

“ZTA-261 has extremely high affinity and selectivity for THRβ among the thyroid hormone derivatives developed to date,” Nambo explained. “In the process of synthesising a variety of derivatives, we have found that precise molecular design is crucial for both selectivity and affinity. We believe that this study will provide new and important insights into drug discovery.”

Source: Institute of Transformative Bio-Molecules (ITbM), Nagoya Universityy

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AI in Healthcare: From Hype to a Game Changing Reality  

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By Margot Brews, Head Health Risk Management Strategy at Momentum Health Solutions

The healthcare sector has been on the cusp of substantial reform for quite some time. However, the introduction and application of artificial intelligence (AI) across various healthcare disciplines will surely stand out as one of the most revolutionary eras in the industry.

This rapidly evolving field has been lauded as the key to unlocking greater quality in healthcare services, introducing more efficient protocols and treatment pathways, as well as considerably increasing access to healthcare across all demographics.

When we place this in a local context, taking into consideration that steps to implement the NHI are already in motion, AI will be critical in helping implement specific elements, such as public health interventions. If we are to refer to the Covid-19 pandemic and its immense scale, AI was leveraged across various countries around the globe to predict the spread of the virus. In doing so, this allowed governments to implement protocols to curb its spread, as well as provide citizens with critical information in an effort to decrease its proliferation.

Looking at the medical schemes sector in South Africa, the industry aims to ultimately improve health outcomes for members and in doing so, encourage and maintain a better quality of life. AI has assisted Momentum Health Solutions in evaluating the delivery of healthcare in the future with clear goals that include increasing access to quality healthcare, and utilising the unmatched innovation that AI offers in assessing member profiles more comprehensively. This is to ensure that we are not only providing a service, but actually understanding in the broadest terms possible what type of care a member requires and partnering with them on that journey.

An example of this is closely analysing commonalities within a member’s treatment pathway. When we review clinical data such as doctors’ consultations, the discipline of the doctor and their particular field of expertise, along with the medication prescribed, we can more timeously start to see patterns developing. This indicates and therefore informs us that the member may have a more serious illness or chronic disease that requires clinical support on a more extensive scale, which we can then discuss with the member and facilitate.

To ensure we are providing tailored healthcare solutions that steer away from offering members generic benefits, we have partnered with Amazon Web Services (AWS), which provides the most comprehensive services, tools, and resources in artificial intelligence today. Through this partnership we have been able to provide members with unique services and individualised care that ultimately ensures their healthcare is a priority.

While AI is indeed key to creating a more efficient healthcare system, ethical considerations remain a concern for many when evaluating factors such as the protection and privacy of data and its ownership, as well as the accuracy of its outputs and conclusions. Having said this, risk mitigation protocols have been implemented to ensure that personal data is protected, and ethical standards are maintained at the highest level.

AI is certainly the most effective solution in the 21st century when investigating ways to solve the ongoing healthcare crisis, particularly in South Africa, where immense disparity exists between the public and private sectors. Leveraging AI, both from a medical scheme provider perspective and more broadly, will not only empower current and future workforces within the sector, but will also create greater opportunity for improved healthcare services that can be sustained. When implemented and utilised for the benefit of all, AI has the potential to be South Africa’s healthcare redeemer.