Month: July 2025

Categories : Diet and Nutrition Metabolic DisordersTags :

A Nighttime Pistachio Snack May Reshape Gut Microbiome in Prediabetes

On By ModernMedia

Eating pistachios every night for 12 weeks altered gut bacteria, according to new study

Photo by Brenan Greene on Unsplash

Prediabetes affects a third of people in the United States and most of them will develop Type 2 diabetes, yet effective dietary intervention strategies remain limited. Pistachios have shown promise in improving markers of diet quality, yet little is known about how they influence the gut microbiome – a key player in glucose regulation and inflammation.

A new study led by Kristina Petersen, associate professor of nutritional sciences at Penn State, determined that nighttime pistachio consumption affects gut bacteria in adults with prediabetes. Though the potential therapeutic implications of the findings remain unclear, according to Petersen, they may prove significant for people who are working to improve their metabolic health.

The findings, published in the journal Current Developments in Nutrition, suggested that replacing a traditional carbohydrate-based bedtime snack with pistachios may reshape the gut microbiome. A previous study by these researchers demonstrated that pistachios have a similar effect on blood glucose as 15 to 30 grams of carbohydrates.

“Pistachios seem to be able to meaningfully shift the gut microbial landscape in adults with prediabetes especially when consumed as a nighttime snack.”

Kristina Petersen, associate professor of nutritional sciences at Penn State

“A common dietary recommendation for individuals with prediabetes is to consume a nighttime snack consisting of 15 to 30 grams of carbohydrates to help regulate overnight and morning blood glucose levels,” said Terrence Riley, lead author of this research who earned his doctorate in nutritional sciences at Penn State and currently works as a postdoctoral research fellow at Louisiana State University. “As an example, you could eat one or two slices of whole grain bread.”

Researchers observed that consuming about two ounces of pistachios each night for 12 weeks resulted in significantly different stool microbial community profiles compared to those who consumed the recommended 15 to 30 grams of a carbohydrate snack. Specific bacterial groups, including Roseburia and members of the Lachnospiraceae family – known as “good” bacteria that produces beneficial short-chain fatty acids like butyrate – were more abundant following the pistachio condition.

According to Petersen, butyrate serves as a primary energy source for colon cells, helps maintain the gut barrier and supports anti-inflammatory processes.  

“Pistachios seem to be able to meaningfully shift the gut microbial landscape in adults with prediabetes especially when consumed as a nighttime snack,” Petersen said. “These microbiome changes may offer other long-term health benefits – potentially helping to slow the development of Type 2 diabetes or to reduce systemic inflammation – which we hope to explore in future research.”

The study involved 51 adults with prediabetes and was conducted over two 12-week periods separated by a break, so the effects of the first part of the trial would not affect the second part. By the end of the study, all participants received both treatments. Stool samples were collected and analysed using 16S rRNA gene sequencing, a technique that can help classify bacteria based on their genetic makeup.

Petersen noted that participants who ate pistachios also experienced reductions in several bacterial groups that have been linked to less favorable metabolic outcomes.

“Levels of Blautia hydrogenotrophica – a bacterium that helps produce compounds that can build up in the blood and harm kidney and heart health – were lower after pistachio consumption,” Petersen said. “Levels of Eubacterium flavonifractor, which breaks down beneficial antioxidant compounds from foods like pistachios, also decreased.”

Petersen added that the strength of this study is the design used – a randomised crossover clinical trial, in which all participants receive both treatments in a randomised order. By including all participants in the pistachio group and the standard care group, the study helped the researchers better understand how specific foods like pistachios can influence the gut microbiome.

While the study demonstrated shifts in gut bacteria, it remains unclear whether these changes directly translate to improvements in health – a question that requires further research, Petersen said.

Source: Pennsylvania State University

Categories : Ethics and Law Healthcare Politics and RegulationsTags :

#InsideTheBox with Dr Andy Gray | Should Pharmaceutical Advertising in SA Be Better Regulated, and Why?

On By ModernMedia
#InsideTheBox is a column by Dr Andy Gray, a pharmaceutical sciences expert at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. (Photo: Supplied)

By Andy Gray

For over 20 years, the law has required that the Minister of Health issues regulations to govern the advertising of medicines in South Africa, but as yet no such regulations are in place. In his latest #InsideTheBox column, Dr Andy Gray considers what this means for the marketing of medicines in the country.

Anyone who has travelled to the United States will have been struck by the extent to which medicines, both those requiring a prescription and those that can be bought by consumers without a prescription, are advertised on television.

The situation in South Africa is quite different. While there are many advertisements for medicines shown on local television stations, only some are specific about the proprietary (brand) name of the medicine and its indications. Other advertisements focus instead on the indication (the reason for using the medicine), but do not identify it by name. Instead, viewers are urged to approach their pharmacies or medical practitioners. At a different time, an advertisement may be flighted which identifies a medicine, its strength, pack size and perhaps price, but provides no information about what the indication for the medicine is.

To what extent does this represent meaningful and justified regulatory control over pharmaceutical marketing?

Only two countries with effective medicines regulatory systems allow prescription-only medicines to be advertised directly to the consumer, these being the United States and New Zealand. Other countries, including South Africa, restrict the advertising of prescription-only medicines to the health professionals who can prescribe or dispense them. One of the key justifications for this restriction on the ability of the pharmaceutical industry to market their products is that direct-to-consumer advertising may result in more inappropriate prescribing, when prescribers are under pressure from patients demanding medicines they have seen advertised. Short television advertisements are unlikely to be able to convey a balanced account of the potential benefits and harms of medicines, especially those that are new to the market.

South African law contains an interesting variant to regulation in this area. General Regulation 42 issued in terms of the Medicines and Related Substances Act, 1965, allows medicines containing substances in Schedules 0 and 1 to be advertised to the public, but requires that those containing substances in Schedules 2 to 6 to be advertised “only for the information of pharmacists, medical practitioners, dentists, veterinarians, practitioners, and other authorised prescribers” or “in a publication which is normally or only made available” to such persons. While Schedule 0 medicines can be bought in any retail outlet, Schedule 1 and 2 medicines can only be obtained from a pharmacy, but not self-selected from a shelf. The justification for that particular cut-off is difficult to trace in any policy document. An amendment to the regulation was published for comment in February 2023, but the final regulation has yet to be issued by the Minister of Health.

‘Failure to follow through’

The fundamental problem, however, lies in a failure to follow through on the legislation previously passed by Parliament. Section 18C of the current version of the Medicines and Related Substances Act, 1965, contains a prescriptive instruction to the Minister. “The Minister shall, after consultation with the relevant industries and other stakeholders, make regulations relating to the marketing of medicines, medical devices or IVDs and such regulations shall also provide for Codes of Practice for relevant industries,” it states. From 2003 to 2017, the section read: “The Minister shall, after consultation with the pharmaceutical industry and other stakeholders, make regulations relating to the marketing of medicines, and such regulations shall also provide for an enforceable Code of Practice.” The expansion of the remit, to include medical devices and in vitro diagnostics (IVDs) was added by Parliament in 2008, but only took effect in 2017.

Photo by Derek Finch

The wording is peremptory – the Minister “shall” – which leaves no room for delay. While the word “enforceable” has been removed, the very intent of a regulation is that it should be enforced. That no regulations have been forthcoming in more than 20 years is an extraordinary failure of governance.

That failure is compounded by another act of omission. Section 18A of the Act states: “No person shall supply any medicine, medical device or IVD according to a bonus system, rebate system or any other incentive scheme.” The law also enables the Minister to “prescribe acceptable and prohibited acts” in this regard, in consultation with the Pricing Committee. No final regulations have been issued since 2017. The Pricing Committee is established to advise the Minister on matters relating to the pricing of medicines, such as the annual maximum increase and the dispensing fees charged by pharmacists and licensed dispensing practitioners.

It is already an offence, in terms of section 29 of the Act, for any person to make “any false or misleading statement in connection with any medicine, Scheduled substance, medical device or IVD”. Regulation 42 also states: “No advertisement for a medicine may contain a statement which deviates from, with or goes beyond the evidence submitted in the application for registration of such medicine with regard to its safety, quality or efficacy where such evidence has been accepted by the Authority in respect of such medicine and incorporated into the approved information of such medicine”.

While these two provisions may prevent false or misleading advertising, they are limited in their scope. In particular, since no complementary medicines are yet registered by the South African Health Products Regulatory Authority (SAHPRA), none have an approved professional information (previously known as a package insert) or a patient information leaflet.

Industry self-regulation

The pharmaceutical and medical devices industries have not been idle during this period of government inaction. A non-profit, self-regulatory body, the Marketing Code Authority (MCA), has developed a Code of Marketing Practice, drawing on international guidelines. This code provides for sanctions when rules are broken, following adjudication of a complaint. Fines of up to a maximum of R500 000 can be levied for severe or serious offences, which would, for example, pose “safety implications for patients”.

However, as a self-regulatory body, the MCA cannot require membership by any licensed manufacturer. It means that those manufacturers which are not members of the MCA are not bound by the Code and cannot be sanctioned. The MCA therefore advocates that compliance with a Code should be a condition to get a license to operate as a manufacturer. The MCA has also responded to draft regulations on perverse incentives.

At a time when deliberate disinformation is being disseminated from many quarters, including from government authorities previously considered to be reliable, a weakened regulatory system cannot simply be allowed to stagger along, in defiance of the express instructions of the legislature. Public safety demands an effective regulatory mechanism to proactively examine pharmaceutical marketing, across all media, the ability to take meaningful action where transgressions are identified, and an even playing field for all actors.

*Dr Gray is a Senior Lecturer at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. This is part of a new series of #InsideTheBox columns he is writing for Spotlight.

Disclosure: Gray is a member of South Africa’s National Essential Medicines List Committee and co-chairs its Expert Review Committee.

Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.

Republished from Spotlight under a Creative Commons license.

Read the original article.

Categories : ExerciseTags :

Just 7000 Steps a Day Still Lead to Health Benefits

On By ModernMedia
Photo by Teona Swift on Unsplash

A major new study led by the University of Sydney suggests that walking 7000 steps a day offers similar health benefits across several outcomes as walking 10 000. Led by Professor Melody Ding from the School of Public Health, the study was published in The Lancet Public Health and analysed data from 57 studies from 2014 to 2025 that were conducted in more than ten countries including Australia, USA, UK and Japan.

The largest and most comprehensive review to date, the researchers examined the impact that different daily step counts have on the chance of dying from cardiovascular disease and cancer, and developing diseases such as cancer, type 2 diabetes, dementia and depression. Professor Melody Ding says the findings offer a more achievable benchmark for people who struggle to meet traditional exercise guidelines. 

“Aiming for 7000 steps is a realistic goal based on our findings, which assessed health outcomes in a range of areas that hadn’t been looked at before,” said Professor Ding.

“However, for those who cannot yet achieve 7000 steps a day, even small increases in step counts, such as increasing from 2000 to 4000 steps a day, are associated with significant health gain.

“We know daily step count is linked to living longer, but we now also have evidence that walking at least 7000 steps a day can significantly improve eight major health outcomes – including reducing risk of cardiovascular disease, dementia and depressive symptoms.”

“Our research helps to shift the focus from perfection to progress. Even small increases in daily movement can lead to meaningful health improvements.”

Professor Melody Ding

Health benefits at different step counts

The researchers looked at studies in which participants wore step counting devices, such as pedometers, accelerometers and fitness trackers, to track their daily step counts. Starting at 2000 steps, experts compared the health outcomes of people walking more steps a day at 1000 step increments to see whether there was any difference in the risk of early death or other major diseases. 

When compared with 2000 steps a day, researchers found that: 

  • Walking 7000 steps a day reduced the risk of death by 47%, which was almost identical to the benefit seen at walking 10 000 steps per day. 
  • Dementia risk dropped by 38% from walking 7000 steps a day, with only a 7 percent extra reduction at 10 000 steps. 
  • Risk of type 2 diabetes fell by 22 percent from walking 10,000 steps a day and reduced to 27 percent at 12,000 steps.
  • Significant health improvements were seen when people increased their average daily steps from 2000 to between 5000 and 7000 steps. 

“For people who are already active, 10,000 steps a day is great,” said Dr Katherine Owen, co-author and chief analyst of the study from the School of Public Health. “But beyond 7000 steps, the extra benefits for most of the health outcomes we looked at were modest.”

The researchers are working with the Australian government to use the evidence from this study to inform future updates to physical activity guidelines.

“Our research helps to shift the focus from perfection to progress. Even small increases in daily movement can lead to meaningful health improvements,” said Professor Ding. 

Experts are calling for future studies to explore how step goals should vary based on age, health status and region, and to include diverse populations and longer-term data to strengthen the evidence. Professor Ding says this kind of detail is rare and will be useful for health practitioners when tailoring advice for patients.

Source: The University of Sydney

Categories : OphthalmologyTags :

Retinal Repair Work is Done by Microglia, not Neutrophils

On By ModernMedia

Findings have implications for understanding what goes wrong in retinal diseases

Photoreceptor cells in the retina. Credit: Scientific Animations

In a new study from the Flaum Eye Institute and Del Monte Institute for Neuroscience at the University of Rochester, researchers have discovered that the retina responds to damage differently than many other tissues in the body. When photoreceptor cells in the retina are damaged, microglia, or the brain’s immune cells, respond, and the neutrophils are not recruited to help despite passing through nearby blood vessels.

“This finding has high implications for what happens for millions of Americans who suffer vision loss through loss of photoreceptors,” said Jesse Schallek, PhD, associate professor of Ophthalmology and senior author of the study published in eLife. “This association between two key immune cell populations is essential knowledge as we build new therapies that must understand the nuance of immune cell interactions.”

Using adaptive optics imaging, a camera technology developed by the University of Rochester that allows the imaging of single neurons and immune cells inside the living eye, researchers studied the retinas of mice with photoreceptor damage. They found that while both neutrophil and microglia cells are present in the retina, only microglia cells respond to photoreceptor injury, and they do not call upon neutrophils to help repair the photoreceptor damage. Researchers believe this suggests a type of cloaking occurs during retinal injury to protect the retina from a rush of immune cells that could do more harm than good.

“What is remarkable here is that the passing neutrophils are so close to the reactive microglia, and yet they do not signal to them to assist in damage recovery,” said Schallek.

“This is notably different than what is seen in other areas of the body where neutrophils are the first to respond to local damage and mount an early and robust response.”

Source: University of Rochester Medical Center

Categories : Genetics Respiratory DiseasesTags :

Scientists Reconstruct the Genome of the 1918 Influenza Virus

On By ModernMedia

Genetic analysis of the early pandemic virus shows key adaptations to humans.

Creative artwork featuring colourised 3D prints of influenza virus (surface glycoprotein hemagglutinin is blue and neuraminidase is orange; the viral membrane is a darker orange). Note: Not to scale. Credit: NIAID

Researchers from the universities of Basel and Zurich have used a historical specimen from UZH’s Medical Collection to decode the genome of the virus responsible for the 1918-1920 influenza pandemic in Switzerland. The genetic material of the virus reveals that it had already developed key adaptations to humans at the outset of what became the deadliest influenza pandemic in history.

New viral epidemics pose a major challenge to public health and society. Understanding how viruses evolve and learning from past pandemics are crucial for developing targeted countermeasures. The so-called Spanish flu of 1918-1920 was one of the most devastating pandemics in history, claiming some 20 to 100 million lives worldwide. And yet, until now, little has been known about how that influenza virus mutated and adapted over the course of the pandemic.

More than 100-year-old flu virus sequenced

An international research team led by Verena Schünemann, a paleogeneticist and professor of archaeological science at the University of Basel (formerly at the University of Zurich) has now reconstructed the first Swiss genome of the influenza virus responsible for the pandemic of 1918-1920. For their study, the researchers used a more than 100-year-old virus taken from a formalin-fixed wet specimen sample in the Medical Collection of the Institute of Evolutionary Medicine at UZH. The virus came from an 18-year-old patient from Zurich who had died during the first wave of the pandemic in Switzerland and underwent autopsy in July 1918.

Three key adaptations in Swiss virus genome

“This is the first time we’ve had access to an influenza genome from the 1918-1920 pandemic in Switzerland. It opens up new insights into the dynamics of how the virus adapted in Europe at the start of the pandemic,” says last author Verena Schünemann. By comparing the Swiss genome with the few influenza virus genomes previously published from Germany and North America, the researchers were able to show that the Swiss strain already carried three key adaptations to humans that would persist in the virus population until the end of the pandemic.

Two of these mutations made the virus more resistant to an antiviral component in the human immune system – an important barrier against the transmissions of avian-like flu viruses from animals to humans. The third mutation concerned a protein in the virus’s membrane that improved its ability to bind to receptors in human cells, making the virus more resilient and more infectious.

New genome-sequencing method

Unlike adenoviruses, which cause common colds and are made up of stable DNA, influenza viruses carry their genetic information in the form of RNA, which degrades much faster. “Ancient RNA is only preserved over long periods under very specific conditions. That’s why we developed a new method to improve our ability to recover ancient RNA fragments from such specimens,” says Christian Urban, the study’s first author from UZH. This new method can now be used to reconstruct further genomes of ancient RNA viruses and enables researchers to verify the authenticity of the recovered RNA fragments.

Invaluable archives

For their study, the researchers worked hand in hand with UZH’s Medical Collection and the Berlin Museum of Medical History of the Charité University Hospital. “Medical collections are an invaluable archive for reconstructing ancient RNA virus genomes. However, the potential of these specimens remains underused,” says Frank Rühli, co-author of the study and head of the Institute of Evolutionary Medicine at UZH.

The researchers believe the results of their study will prove particularly important when it comes to tackling future pandemics. “A better understanding of the dynamics of how viruses adapt to humans during a pandemic over a long period of time enables us to develop models for future pandemics,” Verena Schünemann says. “Thanks to our interdisciplinary approach that combines historico-epidemiological and genetic transmission patterns, we can establish an evidence-based foundation for calculations,” adds Kaspar Staub, co-author from UZH. This will require further reconstructions of virus genomes as well as in-depth analyses that include longer intervals.

Source: University of Zurich

Categories : NeurologyTags :

Why Do We Need Sleep? Oxford Researchers Find the Answer May Lie in Mitochondria

On By ModernMedia

New study uncovers how a metabolic “overload” in specialised brain cells triggers the need to sleep.

Photo by Cottonbro on Pexels

Sleep may not just be rest for the mind – it may be essential maintenance for the body’s power supply. A new study by University of Oxford researchers, published in Nature, reveals that the pressure to sleep arises from a build-up of electrical stress in the tiny energy generators inside brain cells.

The discovery offers a physical explanation for the biological drive to sleep and could reshape how scientists think about sleep, ageing, and neurological disease.

Led by Professor Gero Miesenböck from the Department of Physiology, Anatomy and Genetics (DPAG), and Dr Raffaele Sarnataro at Oxford’s Centre for Neural Circuits and Behaviour, the team found that sleep is triggered by the brain’s response to a subtle form of energy imbalance. The key lies in mitochondria – microscopic structures inside cells that use oxygen to convert food into energy.

When the mitochondria of certain sleep-regulating brain cells (studied in fruit flies) become overcharged, they start to leak electrons, producing potentially damaging byproducts known as reactive oxygen species. This leak appears to act as a warning signal that pushes the brain into sleep, restoring equilibrium before damage spreads more widely.

‘You don’t want your mitochondria to leak too many electrons,’ said Dr Sarnataro. ‘When they do, they generate reactive molecules that damage cells.’

The researchers found that specialised neurons act like circuit breakers – measuring this mitochondrial electron leak and triggering sleep when a threshold is crossed. By manipulating the energy handling in these cells – either increasing or decreasing electron flow – the scientists could directly control how much the flies slept.

Even replacing electrons with energy from light (using proteins borrowed from microorganisms) had the same effect: more energy, more leak, more sleep.

Professor Miesenböck said: ‘We set out to understand what sleep is for, and why we feel the need to sleep at all. Despite decades of research, no one had identified a clear physical trigger. Our findings show that the answer may lie in the very process that fuels our bodies: aerobic metabolism. In certain sleep-regulating neurons, we discovered that mitochondria – the cell’s energy producers – leak electrons when there is an oversupply. When the leak becomes too large, these cells act like circuit breakers, tripping the system into sleep to prevent overload.’

The findings help explain well-known links between metabolism, sleep, and lifespan. Smaller animals, which consume more oxygen per gram of body weight, tend to sleep more and live shorter lives. Humans with mitochondrial diseases often experience debilitating fatigue even without exertion, now potentially explained by the same mechanism.

‘This research answers one of biology’s big mysteries,’ said Dr Sarnataro.

‘Why do we need sleep? The answer appears to be written into the very way our cells convert oxygen into energy.’

The paper, ‘Mitochondrial origins of the pressure to sleep‘, is published in Nature.

Source: University of Oxford

Categories : Cardiovascular Disease Metabolic DisordersTags :

Study Finds Higher Cardiovascular Risk for One Particular Sulfonylurea

On By ModernMedia
Photo by Stephen Foster on Unsplash

New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the US within this category, but not available in South Africa – was linked to higher incidence of heart failure, related hospitalisation and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published in JAMA Network Open.

“Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest,” said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors.”

Turchin and co-authors emulated a target trial by analysing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48 165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those covered by two different national health insurance plans.

The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide) or DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.

“Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits,” said Turchin. 

Source: Mass General Brigham

Categories : Cancer GeneticsTags :

Women of African Ancestry May Be Biologically Predisposed to Early-onset or Aggressive Breast Cancers

On By ModernMedia
Photo by National Cancer Institute

While the incidence of breast cancer is highest for white women, Black women are more likely to have early-onset or more aggressive subtypes of breast cancer, such as triple-negative breast cancer. Among women under 50, the disparity is even greater: young Black women have double the mortality rate of young white women.

Now, research from the University of Notre Dame is shedding light on biological factors that may play a role in this disparity. The study published in iScience found that a population of cells in breast tissues, dubbed PZP cells, send cues that prompt behavioural changes that could promote breast cancer growth.

Funded by the National Cancer Institute at the National Institutes of Health, the study set out to explore what biological differences in breast tissue could be related to early onset or aggressive breast cancers. Most breast cancers are carcinomas, or a type of cancer that develops from epithelial cells. In healthy tissue, epithelial cells form linings in the body and typically have strong adhesive properties and do not move.

The researchers focused on PZP cells as previous studies had shown that these cells are naturally and significantly higher in healthy breast tissues of women of African ancestry than in healthy breast tissues of women of European ancestry. While PZP cell levels are known to be elevated in breast cancer patients in general, their higher numbers in healthy, African ancestry tissues could hold clues to why early-onset or aggressive breast cancers are more likely to occur in Black women.

“The disparity in breast cancer mortality rates, particularly among women of African descent, is multifaceted. While socioeconomic factors and delayed diagnosis may be contributing factors, substantial emerging evidence suggests that biological and genetic differences between racial groups can also play a role,” said Crislyn D’Souza-Schorey, the Morris Pollard Professor of Biological Sciences at Notre Dame and corresponding author of the study.

The study showed how PZP cells produce factors that activate epithelial cells to become invasive, where they detach from their primary site and invade the surrounding tissue.

For example, a particular biological signaling protein known as AKT is often overactive in breast cancers. This study showed that PZP cells can activate the AKT protein in breast epithelial cells, which in part allows them to invade the surrounding environment. PZP cells also secrete and deposit certain proteins outside the cell that guide the movement of breast epithelial cells as they invade.

Overall, the results of the study emphasize multiple mechanisms by which PZP cells may influence the early stages of breast cancer progression and their potential contribution to disease burden.

The researchers also looked at how a targeted breast cancer drug, capivasertib, which inhibits the AKT protein, impacted PZP cells and found it markedly reduced the effects of the PZP cells on breast epithelial cells.

“It’s important to understand the biological and genetic differences within normal tissue as well as tumours among racial groups, as these variations could potentially influence treatment options and survival rates. And consequently, in planning biomarker studies, cancer screenings or clinical trials, inclusivity is important,” said D’Souza-Schorey, also an affiliate of Notre Dame’s Berthiaume Institute for Precision Health and Harper Cancer Research Institute.

Source: University of Notre Dame

Categories : GeneticsTags :

US Self-reported Race and Ethnicity Are Poor Proxies of Genetic Ancestry

On By ModernMedia
Photo by ROCKETMANN TEAM

Genetic ancestry is much more complicated than how people report their race and ethnicity. New research, using data from the National Institutes of Health’s (NIH) All of Us Research Program, finds that people who identify as being from the same race or ethnic group can have a wide range of genetic differences. The findings are reported in the American Journal of Human Genetics, a Cell Press journal.

As doctors and researchers learn more about how genetic variants influence the incidence and course of human diseases, the study of genetic ancestry has become increasingly important. This research is driving the field of precision medicine, which aims to develop individualised healthcare.

People whose ancestors came from the same part of the world are likely to have inherited the same genetic variants, but self-identified race and ethnicity don’t tell the whole story about a person’s ancestors. NIH’s All of Us Research Program was created in part to address this puzzle and to learn more about how genetic ancestry influences human health.

In the current study, the investigators looked at the DNA of more than 230 000 people who have volunteered to share their health information for All of Us. They compared it to other large DNA projects from around the world using a technique called principal component analysis (PCA) to visualize population structure and help identify genetic similarity between individuals and groups of people. This analysis showed that people in the US have very mixed ancestry, and their DNA doesn’t always match the race or ethnicity they write on forms. Instead of falling into clear groups based on race or ethnicity, people’s genetic backgrounds show gradients of variation across different US regions and states.

This is especially significant for people who identify as being of Hispanic or Latino origin. These people have a wide-ranging blend of ancestries from European, Native American, and African groups. Importantly, genetic ancestry among these people varies across the US in part because of historic migration patterns. For example, Hispanics/Latinos in the Northeast are more likely to have Caribbean (and thus African) ancestry, and those in the Southwest are more likely to have Mexican and Central American (and thus Native American) ancestry.

One specific discovery was that ancestry was significantly associated with body mass index (BMI) and height, even after adjusting for socio-economic differences. For example, West and Central African ancestries were associated with higher BMI, whereas East Africa ancestry was associated with lower BMI. There were similar findings showing that people with ancestral origins from different parts of Europe have different body measurements including height, with northern European ancestry associated with greater height and southern European ancestry associated with shorter height. This suggests that subcontinental differences in ancestry can have opposite effects on biological traits and diseases.

This finding suggests that the subcontinental differences in ancestry between individuals can have opposite effects on biological traits, diseases, and health outcomes, emphasizing the importance of not classifying individuals into broad ancestry groups such as African, European, or Asian. Doing this will help to make this research more accurate and will help to improve the field of precision medicine.

Source: EurekAlert!

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

How Obesity also Affects the Next Generation

On By ModernMedia

Study reveals why children of obese mothers are more likely to develop metabolic disorders

Metabolites – from the mother permanently reprogram Kupffer cells. This changes their function, causes liver cells (hepatocytes) to accumulate fat and ultimately leads to a fatty liver. The graphic was created with BioRender.com (http://BioRender.com). © Image: AG Mass/University of Bonn

Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn published in the journal Nature offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans.

The team focused on the so-called Kupffer cells. These are macrophages that help protect the body as part of the innate immune system. During embryonic development, they migrate into the liver, where they take up permanent residence. There, they fight off pathogens and break down ageing or damaged cells.

“But these Kupffer cells also act as conductors,” explains Prof Dr Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

Changing the tune: From Beethoven to Vivaldi

It appears, however, that it is this conducting function that is changed by obesity. This is what mouse experiments carried out by Mass in cooperation with other research groups at the University of Bonn suggest. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”

The cause of this disorder seems to be a kind of “reprogramming” of the Kupffer cells in the offspring. As a result, they send out molecular signals that instruct the liver cells to take up more fat. Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi.

This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”

No fatty liver without the molecular switch

When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.

If new treatment approaches emerge from this, it would be good news. The altered behaviour of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause increasing numbers of hepatocytes to die and be replaced with scar tissue, resulting in fibrosis. At the same time, the risk that hepatocytes degenerate and become cancerous increases.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”

Source: University of Bonn