Researchers have discovered a protein marker to help identify cells able to repopulate in patients with damaged blood vessels. Their findings, recently published in Circulation, could lead to new therapies for people with endothelial dysfunction, a type of disorder that contributes to coronary artery disease that may occlude with plaque and lack ability to carry sufficient blood into the heart tissue causing a heart attack.
“This study is the first to establish that a single, prospective marker identifies vascular clonal repopulating endothelial cells (CRECs),” said Chang-Hyun Gil, PhD, MS, assistant research professor of surgery at the Indiana University School of Medicine and co-first author of the study. “These exciting findings could lead to new cell therapies for repair of damaged vessels for patients.”
The researchers analyzed the potential of endothelial cells, which make up the protective inner layer of blood vessels, that express a protein called ABCG2 to make colonies, self-renew and form vessels. These cells could form new blood vessels and contributed to the repair of heart tissue blood vessels after a heart attack.
“By analyzing the genes and proteins in these cells, we identified specific pathways involved in blood vessel formation and tissue regeneration,” Gil said. “We discovered that ABCG2 involved in blood vessel development are more active in these cells compared to others, suggesting these specific endothelial cells have the potential to be used in repairing damaged blood vessels. AbcCRECs are becoming an important cell type to be considered for use in human patients suffering from a variety of diseases such as peripheral arterial disease, diabetes, diabetic proliferative retinopathy, acute kidney disease and cardiovascular disease.”
“It is particularly important that this protein marker identified the CRECs in both mouse and human subjects,” said Mervin C. Yoder, MD, Distinguished Professor Emeritus at the IU School of Medicine and a professor of surgery at the University of Pittsburgh. “Few markers have been found that permit prospective isolation of endothelial cells with reparative properties in both mice and humans, making these findings exciting for future study.”
The team has been studying these types of endothelial cells for more than seven years. Further experiments and studies are needed to better understand the functions and mechanisms of AbcCRECs. This will help in developing methods to apply these cells in treating vascular damage and diseases. Additionally, clinical trials are required to validate the therapeutic efficacy of AbcCRECs and explore how to apply the treatment to patients.

According to a recent Finnish study, high levels of sedentary behaviour and physical inactivity from childhood strain the heart in adolescence. High cardiac workload predicts heart failure and other heart diseases. In light of the findings, increasing moderate and vigorous physical activity from childhood onwards is particularly important in preventing heart diseases.
In a collaborative study by the Faculty of Sport Sciences at the University of Jyväskylä and the Institute of Biomedicine at the University of Eastern Finland, sedentary behaviour and physical activity were followed from childhood to adolescence for eight years. The study showed that adolescents accumulating high levels of sedentary behaviour and low levels of moderate to vigorous physical activity from childhood onwards had a higher cardiac workload in adolescence. Cardiac workload was particularly high in adolescents accumulating low levels of vigorous physical activity.
In addition, high levels of sedentary behaviour and low levels of physical activity were associated with a higher total body fat percentage. Body fat percentage partly explained the associations between sedentary behaviour, physical activity, and cardiac workload. Light physical activity was not associated with cardiac workload.
The results emphasise the importance of increasing physical activity, especially moderate and vigorous activity, reducing sedentary behaviour, and preventing overweight from childhood to prevent heart diseases.
“Youth spend nine to ten hours a day being sedentary,” says Dr. Eero Haapala from the Faculty of Sport and Health Sciences at the University of Jyväskylä, “and only one in ten adolescents accumulated 60 minutes of daily moderate to vigorous physical activity. These are worrying figures.”
“High levels of daily moderate to vigorous physical activity should be a normal part of childhood and adolescence as it improves heart health, but also general well-being,” Haapala emphasises.
The study is based on the ongoing Physical Activity and Nutrition in Children (PANIC) study conducted at the Institute of Biomedicine at the University of Eastern Finland. Sedentary behaviour and physical activity levels were followed for eight years from childhood to adolescence in 153 adolescents. Heart function and strain were measured in adolescence. The study was published in the Journal of the American Heart Association.

Some of the final work of a late University of Virginia School of Medicine scientist has opened the door for life-saving new treatments for solid cancer tumors, including breast cancer, lung cancer and melanoma.
Prior to his sudden death in 2016, John Herr, PhD, had been collaborating with UVA Cancer Center’s Craig L. Slingluff Jr., MD, to investigate the possibility that a discovery from Herr’s lab could help treat cancer.
Eight years of research has borne that idea out: Herr’s research into the SAS1B protein could lead to “broad and profound” new treatments for multiple cancers, many of which are very difficult to treat, Slingluff reports in a new scientific paper in the Journal for ImmunoTherapy of Cancer. Herr is listed as a senior author on the paper.
“John was very excited about this protein SAS1B to be a valuable new target on human cancers, and I am delighted that our findings together further support his hope to make such a difference,” said Slingluff, a surgical oncologist and translational immunologist at UVA Health and the UVA School of Medicine. “The work we published included work done by Dr. Herr and his team over a period of years, as well as our subsequent work together; so, I am glad that the journal agreed with our request to include John as a senior author.”
Promising New Cancer Target
Herr’s lab was not originally focused on cancer — he was the head of UVA’s Center for Research in Contraceptive and Reproductive Health. In that role, he developed the first home fertility test for men, SpermCheck, which is available in pharmacies across the country. But his discoveries about the SAS1B protein found in developing eggs in women could pave the way for new cancer immunotherapies.
While SAS1B is found inside female reproductive cells called oocytes, it is also found on the surface of many different solid cancer cells, Slingluff’s new research verifies. Importantly, it did not appear on the surface of any of the other normal cells Slingluff’s laboratory tested. That suggests that doctors may be able to develop use antibody-based immunotherapy — such as antibody-drug conjugates or CAR T-cell therapy, a strength of UVA Health — to attack the cancer cells while sparing healthy tissue.

“Selectively targeting SAS1B has the potential to have broad and profound impact on the treatment, and therefore reduction in mortality, of multiple malignancies,” Slingluff and his colleagues write in their new paper.
While much more work needs to be done, the new findings are promising. If the approach is successful, it could be a big step forward in cancer care. Many solid-organ cancers are extremely difficult to treat, and patients often have few good treatment options, Slingluff notes.
“Immune therapy is revolutionizing treatment of human cancers,” Slingluff said. “But some cancers have been particularly resistant to immune therapy because of the lack of good targets on those cancers. We hope that this work that John Herr started will bring new hope to patients with those cancers.”
Finding new ways to improve cancer care is a foundational mission of UVA Cancer Center, one of only 56 cancer centers to receive “comprehensive” designation from the National Cancer Institute. The designation honors elite cancer centers with the most outstanding cancer care and research programs in the country.
Advancing the field of immunotherapy is also a key mission of UVA’s forthcoming Paul and Diane Manning Institute of Biotechnology. Now under construction at Fontaine Research Park, the institute is poised to accelerate the development of new treatments and cures for a wide variety of diseases, ultimately transforming how healthcare is delivered across Virginia and beyond.

A new study that followed a cohort of more than 110,000 people establishes significant disparities in the risk of anal cancer for people with HIV and for men who have sex with men with HIV, depending on the region of the country they live in.
It’s known that people with HIV have the highest risk of anal cancer, said lead author Ashish A. Deshmukh, Ph.D., co-leader of the Cancer Control Research Program at MUSC Hollings Cancer Center.
But this study, published in the Journal of the National Cancer Institute on May 7, is the first to show vast geographic disparities in anal cancer risk and an association with opportunistic illnesses and co-morbidities, like diabetes, chronic kidney disease and cardiovascular disease, for people with HIV.
Almost all cases of anal cancer are caused by the human papillomavirus (HPV). It seems that there’s some as-yet-unknown effect, such as inflammation, in people with co-morbidities that allows the HPV to gain a foothold and cause cancer to develop, the paper notes.
People with HIV have a greater relative risk of anal cancer compared with people without HIV, no matter where they live. But the study showed that the relative risk varies across the country — it’s higher for people with HIV in the Midwest or South than the West or Northeast.
“In the Northeast, the risk for people with HIV compared to people without HIV is 16-fold higher,” Deshmukh said. “But for people with HIV in the Midwest, the risk increases to almost 47.5-fold, reaching nearly 100-fold for men who have sex with men with HIV.”
Deshmukh has a few preliminary theories about the causes of these differences but cautioned that this study doesn’t attempt to determine the reasons.

“The objective was to understand whether there are disparities and what may be important risk factors,” he said. The results of this study provide the foundation for further research into the causes underlying these disparities.
However, he noted that screening rates for anal cancer are relatively higher in the Northeast and West. New York state, for example, stands out as the only state with established guidelines for anal cancer screening, a rarity given the absence of national guidelines and the lack of specific protocols in other states for this relatively rare cancer, among the general population.
Various professional societies have begun to develop screening guidelines. In fact, Deshmukh contributed to the recent International Anal Neoplasia Society’s consensus guidelines, published in January.
Those guidelines started with the premise of beginning screening at specific ages based on risk — for example, beginning screening at age 35 for men with HIV who have sex with men and 45 for women with HIV and other men with HIV.
However, this new study suggests that guidelines should consider risk factors like previous opportunistic illnesses or having had a CD4 count below 200. CD4 count is the number of CD4 T-cells, a type of white blood cell, in the blood. A count above 500 is considered healthy, but a count below 200 can trigger an AIDS diagnosis.
Deshmukh said that he hopes to see the U.S. Preventive Services Task Force develop guidelines for anal cancer screening. The task force previously determined that there wasn’t enough information about the risk-benefit balance of anal cancer screening to issue guidelines, Deshmukh said.

However, his ongoing research will provide direct evidence quantifying the potential harms versus benefits of screening for anal cancer among people with HIV.
“We hope that the U.S. Preventive Services Task Force will again take on this topic and evaluate the evidence once we have more data on the harms and benefits of anal cancer screening,” he said.
The current paper notes that anal cancer among people with HIV appears to be on the decline. However, it warns that geographic disparities could increase if the differences in screening activity remain.
This work was supported by grants from the National Institutes of Health and the Canadian Institues of Health Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Centers for Disease Control and Prevention.

Fatty liver disease often leads to chronic liver inflammation and can even result in liver cancer. Scientists from the German Cancer Research Center (DKFZ) and the University of Tübingen have now shown in mice* that intermittent fasting on a 5:2 schedule can halt this development. The fasting regime reduces the development of liver cancer in mice with pre-existing liver inflammation. The researchers identified two proteins in liver cells that are jointly responsible for the protective effect of fasting. An approved drug can partially mimic this effect.
The most common chronic liver condition is non-alcoholic fatty liver disease. It can have serious consequences: If left untreated, it can lead to liver inflammation (metabolic dysfunction-associated steatohepatitis, MASH), liver cirrhosis and even liver cancer. Fatty liver disease is largely considered to be a direct consequence of obesity. It is not only people in Europe and the USA who have put on enormous amounts of weight in recent decades; obesity is also becoming increasingly widespread in emerging countries such as India and China. As a result, the number of cases of liver failure and liver cancer is rising sharply in the countries affected.
“The vicious circle of an unhealthy diet, obesity, liver inflammation and liver cancer is associated with major restrictions and suffering for those affected and also represents a considerable burden on healthcare systems,” says Mathias Heikenwälder, DKFZ and University of Tübingen. “We have therefore investigated whether simple dietary changes can specifically interrupt this fatal process.”
Intermittent fasting has already been shown in several studies to be an effective means of reducing weight and alleviating certain metabolic disorders. Heikenwälder’s team has now tested in mice whether this approach can also protect the liver from fatty degeneration and chronic inflammation.
Resistance to liver inflammation is independent of calorie intake
The animals were fed with a high-sugar and high-fat diet correspondind to the typical Western diet. One group of mice had constant access to the food. As expected, these animals gained weight and body fat and developed chronic liver inflammation.
The mice in the other group were given nothing to eat on two days a week (5:2 intermittent fasting, or 5:2 IF for short), but were allowed to eat as much as they wished on the other days. Despite the high-calorie diet, these animals did not put on weight, showed fewer signs of liver disease and had lower levels of biomarkers that indicate liver damage. In short, they were resistant to the development of MASH.

Interestingly, resistance to the development of a fatty liver was independent of the total calorie intake, as the animals immediately made up for the lost rations after the end of the fasting periods.
When experimenting with different variants of intermittent fasting, it was found that several parameters determine protection against liver inflammation: The number and duration of fasting cycles play a role, as does the start of the fasting phase. A 5:2 dietary pattern works better than 6:1; 24-hour fasting phases better than 12-hour ones. A particularly unhealthy diet requires more frequent dieting cycles.
Heikenwälder’s team now wanted to find out the molecular background of the response to fasting. To this end, the researchers compared protein composition, metabolic pathways and gene activity in the liver of fasting and non-fasting mice. Two main players responsible for the protective fasting response emerged: the transcription factor PPARα and the enzyme PCK1. The two molecular players work together to increase the breakdown of fatty acids and gluconeogenesis and inhibit the build-up of fats.
“The fasting cycles lead to profound metabolic changes, which together act as beneficial detoxification mechanisms and help to combat MASH,” says Heikenwälder, summarizing the molecular details.
The fact that these correlations are not just a mouse phenomenon was shown when tissue samples from MASH patients were examined: Here, too, the researchers found the same molecular pattern with reduced PPAR α and PCK1. Are PPAR α and PCK1 actually responsible for the beneficial effects of fasting? When both proteins were genetically switched off simultaneously in the liver cells of the mice, intermittent fasting was unable to prevent either chronic inflammation or fibrosis.
The drug pemafibrate mimics the effects of PPARα in the cell. Can the substance also mimic the protective effect of fasting? The researchers investigated this question in mice. Pemafibrate induced some of the favorable metabolic changes that were observed with 5:2 fasting. However, it was only able to partially mimic the protective effects of fasting. “This is hardly surprising, as we can only influence one of the two key players with pemafibrate. Unfortunately, a drug that mimics the effects of PCK1 is not yet available,” explains Mathias Heikenwälder.

Intermittent fasting as liver therapy
While Heikenwälder and his team initially focused on the effects of intermittent fasting on the prevention of MASH, they then investigated whether the 5:2 diet could also alleviate existing chronic liver inflammation.
To this end, the team examined mice that had developed MASH after months of being fed a high-sugar, high-fat diet. After a further four months of 5:2 intermittent fasting (on the same diet), these animals were compared with the non-fasting control group. The fasting mice had better blood values, less fatty liver and liver inflammation and above all: they developed less liver cancer and had fewer cancer foci in the liver.
“This shows us that 5:2 intermittent fasting has great potential — both in the prevention of MASH and liver cancer, as well as in the treatment of established chronic liver inflammation,” summarizes principal investigator Heikenwälder. “The promising results justify studies in patients to find out whether intermittent fasting protects against chronic liver inflammation as well as in the mouse model.”
The 5:2 fasting regimen is popular. It is considered comparatively easy to integrate into everyday life, as the fasting days can be tailored to personal needs and no specific foods are prohibited. “Nevertheless, there will always be people who can’t stick to a strict diet in the long term,” says Heikenwälder. “That’s why we want to continue to investigate which combinations of drugs we can use to fully mimic the protective effects of fasting.”
Publication:
Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, Jan Kosla, Xin Li, Enrico Focaccia, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Florian Mueller, Jenny Hetzer, Danijela Heide, Tim Machauer, Nisar P. Malek, Thomas Longerich, Adam J. Rose, Susanne Roth, Johannes Schwenck, Christoph Trautwein, Mohammad M Karimi, Mathias Heikenwälder: PPAR alpha agonist pemafibrate recapitulates aspects of hepatic fasting response
* Why was it necessary to study mice for this experiments?
A high-calorie, unbalanced diet and a sedentary lifestyle are contributing to the sharp rise in the proportion of obese people in many parts of the world. Obesity also increases the risk of a whole range of secondary diseases for those affected, including cardiovascular diseases, metabolic diseases, cancer and joint problems. Understanding these correlations and, ideally, intervening in a targeted manner is an extremely important research goal.
Several organs and organ systems are jointly involved in the development of obesity-related health consequences. The liver, pancreas, brain, lymphatic organs and fatty tissue work together here, which cannot be simulated in the culture dish. The intestine can also play a role in the development of MASH. The spontaneous development of liver cancer from a fatty liver can therefore only be recapitulated and investigated if all these factors interact.
Also crucial is the influence of immune cells that migrate from the periphery of the body into the fatty liver, are activated there and migrate back into the body, where they interact with the fatty tissue. This can only be investigated in an intact organism. Experiments with mice are also necessary to understand which length of fasting periods achieves the most favorable health results in the context of the circadian (day/night) rhythm.

As much as we might not want to think about it, mucus is everywhere in our bodies. It coats our airways and our digestive systems and serves as a first line of defense against pathogens, a habitat for our microbiomes, and a conveyor belt for our insides to keep everything moving smoothly.
The front-line role of mucus means it is often the site of the first symptoms of infection or disease. Understanding how mucus changes, and what it changes in response to, can help diagnose illnesses and develop treatments. Designing a study to measure the physical properties of mucus, however, is nothing to sneeze at.
In APL Bioengineering, by AIP Publishing, researchers from Stanford University developed a system to grow mucus-producing intestinal cells and study the characteristics of the mucus in different conditions. Their platform can explore the effects of pathogens and help develop medications to combat them.
Currently, researchers looking to study intestinal mucus commonly use lab animals for their experiments. These animals would be given a pathogen or drug, and researchers would surgically remove the intestinal mucus to study the effects. This process is expensive, complex, and most importantly, deeply unpleasant for the animals.
In addition, the researchers say, the act of removing the mucus is likely to change how it behaves, making any obtained results unreliable.
“When people collect the mucus from the animal, they’ll pipette it off or scrape it off,” said author Margaret Braunreuther. “But what we found is that when we pipette the mucus layer from our cell culture, we see a very different behavior after that action. We think that the act of pipetting or scraping this very soft polymeric solution is resulting in more liquidlike behavior.”
The alternative process developed by the Stanford team involves growing a layer of intestinal cells on a laboratory plate exposed to air. These cells produce a layer of mucus that the researchers can easily access for testing. Using a magnetic wire, they could measure the consistency of the mucus without affecting its properties.

“We put this wire on the mucus layer of the live cells, and then we applied a magnetic force to this probe and measured its displacement,” said Braunreuther. “From the relationship between the applied force and the magnetic wire displacement, we can then calculate the rheological properties of the material.”
Using this setup, the team simulated an infection by a parasitic worm to observe how the mucus responds. This study serves as both a practical demonstration of their platform and a glimpse into how these infections could be treated.
The group is now exploring even more ways to leverage their approach for better mucus health.
“We have a parallel effort to study airway mucus, looking at conditions such as cystic fibrosis and acute asthma,” said author Gerald Fuller. “We also started a collaboration with a group in Berlin to develop drugs to restore a healthy mucus response.”

Understanding how cancerous cells spread from a primary tumor is important for any number of reasons, including determining the aggressiveness of the disease itself. The movement of cells into the extracellular matrix (ECM) of neighboring tissue is an essential step in cancer progression that directly correlates to the onset of metastasis.
In APL Bioengineering, by AIP Publishing, a team of researchers from Germany and Spain used a breast cancer cell line panel and primary tumor explants from breast and cervical cancer patients to examine two different cellular contractility modes: one that generates collective tissue surface tension that keeps cell clusters compact and another, more directional, contractility that enables cells to pull themselves into the ECM.
“We focused on two parameters, namely the ability of the cells to pull on the ECM fibers and generate traction forces and on their ability to pull on each other, thereby generating a high tissue surface tension,” said author Eliane Blauth. “We linked each property to different contractile mechanisms and asked how they are connected to cancer cell escape and tumor aggressiveness.”
The team found that more aggressive cells pull more strongly on the ECM than on themselves while noninvasive cells pull more strongly on themselves than on the ECM — and that the different pulling behaviors are attributed to different structures of actin cytoskeleton inside the cells. Invasive cells use predominantly actin stress fibers — thick actin bundles that span the cell — to generate forces on their surroundings, while noninvasive cells generate forces through their actin cortex, a thin network directly under the cell membrane.
The study showed it is not the overall magnitude of these contractility modes but the interplay between them that determines a cell’s potential for escape. Experiments with only moderately invasive cells demonstrated the total force these cells generate on the ECM fibers is comparable to that of noninvasive cells, yet they can still detach and invade the ECM, which is not possible for noninvasive cells.
“The noninvasive cells still have a high cortical contractility, keeping them together, while the moderately invasive cells have a nearly disappearing cortical contractility,” said Blauth. “So not much is holding them back even though they pull much weaker on the ECM fibers.”
The team’s measurements with patient-derived vital tumor explants confirmed their findings from the cell line experiments. Here, the number of cells with a high cortical contractility decreased during tumor progression.
“This further indicates that the ability of the cells to pull on each other and hold themselves clustered together becomes weaker as the tumor grows, potentially increasing metastasis risk.”

A new computational model simulating fruit fly wing development has enabled researchers to identify previously hidden mechanisms behind organ generation.
Because organs develop in remarkably similar ways in fruit flies and people, biological insights from this model can be used to inform the diagnosis and treatment of human diseases such as cancer, Alzheimer’s and congenital genetic birth defects.
Jeremiah Zartman, associate professor of chemical and biomolecular engineering at the University of Notre Dame, worked with a multidisciplinary research team that included collaborators from the University of California, Riverside to develop a fruit fly model to reverse engineer the mechanisms that generate organ tissue.
The team’s findings, which offer a deeper understanding of the chemical and mechanical levers regulating organ cell size and shape, have been published in Nature Communications.
“We’re trying to simulate an organ in the computer — effectively creating a digital twin of that organ,” Zartman said. “We’re taking the different cells and parts of cells to see if we can predict how they will interact with each other.”
Organs develop in response to what Zartman calls a “symphony” of signals. The researchers’ fruit fly model integrates the numerous signals that orchestrate cell movement, contraction, adhesion and proliferation. It also incorporates the mechanical, chemical and structural properties of cell components and accounts for how these properties change over time and in different locations.
Both the model and his lab’s experimental results showed that there were two distinct classes of chemical signaling pathways, or sequences of signals, that produce either curved or flat tissues — identifying the flexibility and tunability of generating an organ of a specified shape.

Cells receiving signals from insulin led to an increase in the curvature of the tissue, while cells receiving inputs from two other key growth regulators flattened tissue. The researchers discovered that these growth regulators also manipulated the cell’s internal framework, or cytoskeleton, to further sculpt cell size and shape.
The Zartman group’s big-picture goal is to identify the extent to which the biological rules gleaned from simulated fly organ studies are shared with systems as distinct as plants, fish and humans.
“Our goal for the future is to develop a digital prototype organ that tackles a fundamental question in biology — how do cells generate functional organs?” Zartman said.
The team’s ongoing work is funded by National Science Foundation’s Emergent Mechanisms in Biology of Robustness, Integration & Organization (EMBRIO) Institute as well as the Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS) program.

In one of the first studies of its kind, UC Santa Barbara researchers have found that the immune status of postpartum mothers shifts with how she feeds her baby. According to a paper published in the journal Scientific Reports, certain inflammatory proteins — substances that are secreted as part of an immune response — peak at different times of day, correlating with whether the mothers breastfeed, pump or formula-feed their babies.
“It’s a great study; there are so many unanswered questions about maternal health in the postpartum period,” said Amy Boddy, a human biologist and evolutionary theorist at UCSB’s Department of Anthropology, and senior author of the paper. It’s a rare deep look at immunity from the postpartum mother’s perspective, which she hopes will become a springboard for future research.
Indeed, she said, much of the research on the effects of breastfeeding concentrate on the infant, with many findings that demonstrate benefits of breastfeeding to the baby’s immunity and development. In the longer term, mothers who have breastfed also have a lower risk for developing certain cancers and diabetes.
But how about women within the crucial first months to years after childbirth? To investigate, Boddy, lead author and co-Principal Investigator Carmen Hové and team followed a population of 96 women in the Seattle area who had given birth within the previous six months and collected their saliva twice over a 24-hour period, once before going to bed, and again in the morning after waking. Because the COVID-19 pandemic had just hit and everyone was on lockdown, the researchers found themselves with an unexpectedly ideal experimental situation, in which the mothers’ environments were heavily controlled for infections which could confound the immunity readings.
“It was kind of a perfect natural experiment, because we’re looking at immune function and of the reports, no one was sick,” Boddy said. The goal? To follow cyclical levels of five types of proteins (labeled CRP, IL-1β. IL-6, IL-8 and TNF-α) that indicate inflammation that is a marker of immune response.
“It’s been shown before that breastfeeding has a suite of inflammatory responses to it,” Boddy explained. “Inflammation isn’t always a bad thing — the breast is remodeling, functioning and doing things in the body.” The proteins’ diurnal patterns meant that generally speaking, concentrations are typically higher in the mornings and lower in the evenings. What the researchers were interested in was seeing out-of-the-ordinary levels in the normal ebb and flow of these proteins and how they matched up with the new mothers’ infant feeding strategies.
For several proteins, there were no measurable deviances in the morning and evening levels no matter whether the mothers pumped or breastfed. However, for the C-reactive protein (CRP) the researchers found that levels peaked in the evenings for women who relied heavily on breastfeeding, reversing the normal diurnal trend.

“We expected that low rates of lactating would be associated with a relatively high morning peak in CRP and vice versa,”Hové said. “What we ended up finding is that among mothers who reported intensive lactation, via either breastfeeding or pumping, CRP was higher at nighttime.” More research is needed to determine the precise effects of this unique pattern in breastfeeding or lactating mothers, she added.
“We don’t know exactly what’s going on here,” Boddy said, “maybe not emptying your breast fully, leads to inflammation.” Or maybe it’s the other direction, and the inflammation is a healing response from pregnancy. Maybe the incomplete emptying is a change of behavior due to stress. Perhaps the stress is the result of interrupted sleep that comes with round-the-clock breastfeeding schedules. “We don’t have the causal arrow of what’s going on; it’s just an association,” she said. “This study shows that there is a unique immune profile, and we should study this in more detail.”
What this study reveals is the true complexity of postpartum breastfeeding. Breastfeeding is part of an ongoing physiological negotiation between mother and the new baby which favors the infant, Boddy said.
“There’s something in evolutionary biology called maternal-fetal conflict. The idea is, when you’ve two bodies in one maternal unit, that the baby always wants a little more than the mother has to give,” she explained. This research dives into the gray area of postpartum health from the mother’s perspective, particularly in the realm of breastfeeding and immunity.
Indeed, despite the ideal, long promoted by institutes such as the World Health Organization that “breast is best,” the researchers found that even from their sample of educated, relatively affluent women, there existed a combination of lactation feeding strategies, highlighting challenges of exclusive at-the-nipple feeding.
“There’s been a lot of pushback, mostly from lactating mothers, centered around time constraints. Our society doesn’t make it easy for us to actually breastfeed and have lactational support,” said Boddy, who nursed both her children as infants and found it “challenging to meet breastfeeding goals.” In addition, the guidelines aren’t clear on when breastfeeding should end. When do the physiological and other benefits diminish for the mother in this ongoing negotiation, which could last years? Could this information yield some insight on other trends, such as maternal mortality?
The researchers hope to study the topic more deeply, and on a more individual level, to tease out further patterns in postpartum health and breastfeeding, such as with the various hormones involved in lactation.
“I think this study has opened up more questions than what we’ve answered. What we would like to do is follow some of these same women throughout the course of their postpartum experience,” Boddy said. “It’s always been challenging to find the best way of feeding our babies and breastfeeding is so demanding.”

The world’s largest study of cerebral palsy (CP) genetics has discovered genetic defects are most likely responsible for more than a quarter of cases in Chinese children, rather than a lack of oxygen at birth as previously thought.
The study, published in the scientific journal, Nature Medicine used modern genomic sequencing and found mutations were significantly higher in CP cases with birth asphyxia, indicating a lack of oxygen could be secondary to the underlying genetic defect. The results are consistent with smaller studies globally.
More than 1,500 Chinese children with CP were involved in this research project, which was a collaborative effort between the University of Adelaide and Fudan University Shanghai, Zhengzhou University, Zhengzhou and associates.
The Australian team was led by obstetrician and University of Adelaide’s Emeritus Professor Alastair MacLennan AO and human geneticist, Professor Jozef Gecz.
“24.5 per cent of Chinese children in the study had rare genetic variations linked to cerebral palsy. This revelation mirrors our earlier findings in our Australian cerebral palsy cohort, where up to one third of cases have genetic causes,” said Professor Gecz, who is the University of Adelaide’s Head of Neurogenetics at the Adelaide Medical School and the Robinson Research Institute.
“Our research shows at least some babies who experience birth asphyxia and are diagnosed with CP may have improper brain development as a result of the underlying genetic variants rather than a lack of oxygen.
“Crucially, clinically actionable treatments were found in 8.5 per cent of cases with a genetic cause. It is exciting to see how genetic pathways to cerebral palsy inform tailored treatments for these individuals.”
Cerebral palsy affects movement and posture and is the most common motor disability in children. The disorder is diagnosed in up to 2 per 1000 children globally and is sometimes in association with epilepsy, autism and intellectual difficulties. Symptoms often emerge during infancy and early childhood and can range from mild to severe.

The research team identified 81 genes with causation mutations in the children with CP. These genes are known to play important roles in neural and embryonic development and may affect the molecular pathways responsible for respiration.
“A lack of oxygen at birth is often claimed to be the cause of CP in medical litigation following a diagnosis and this has led to the presumption that the condition is preventable with better obstetrics or midwifery. This is simply not the case,” said Professor MacLennan, who has spent the past 30 years advocating that there is little scientific evidence to support the myth that cerebral palsy is due to trauma or lack of oxygen at birth.
Professor MacLennan said frequent litigation has been associated with a high increase in “defensive” caesarean delivery and high insurance premiums for obstetricians.
“These results highlight the need for early genetic testing in children with cerebral palsy, especially those with risk factors like birth asphyxia, to ensure they receive the right medical care and treatment.
“All children with cerebral palsy merit modern genetic screening as early and customised interventions really can make a difference and improve their long-term outcomes,” he said.
Ongoing genetic research is also investigating other types of contributing genetic variation to the cause of CP and, as a result, the researchers expect that the overall genetic diagnosis rate is likely to increase.