Breast cells in breastmilk are alive and may offer insights into breast cancer

 

• Medical researchers have assumed that breast cells found in breast milk were dead or dying, but a recent study shows these cells are alive and can be isolated and studied.
• Genetic analysis of these cells has revealed two cell populations responsible for secreting breast milk in human breasts, whereas previously there was assumed to be just one as observed in mice.
• Future studies of these cells could provide insight into how breast cancer originates and how breastfeeding could protect some individuals.

The protective effect of breastfeeding against breast cancer has been known for some time. However, the mechanisms underlying this have remained unclear.

While mouse studies suggest this could be due to changes in the breast tissue that occur during and breastfeeding causing long lasting epigenetic changes, it has been difficult to investigate. This is because most breast tissue donors are people undergoing surgery and very few of these individuals would have been lactating.

During breastfeeding, some of the cells from the surface of the milk glands inside the breast are expelled into the breast milk itself. While it was not clear how much insight they could provide as scientists had previously assumed them to be dead or dying, a recent study by a team from the Wellcome-MRC Cambridge Stem Cell Institute (CSCI) and the Department of Pharmacology at the University of Cambridge, UK, has shown that these remain alive in the milk and can be isolated from expressed breast milk.

In a paper in Nature Communications, the team outlined their findings by analyzing these breast cells for the first time.

Karis Betts, health information manager at Cancer Research UK — who was not involved in the research — told Medical News Today in an email:

“Current research suggests a link between breastfeeding and reduced risk of breast cancer. Not all questions have been answered about why this is and how it affects different groups of women and different types of breast cancer. It’s thought that hormonal changes, impact on ovulation, and changes to the cells in the breast might play a role.”

“This early-stage research shows the difference between cell types present when lactating and not, which helps paint the picture of what these cell changes might be. But the study can’t tell us which of these changes, if any, are linked to breast cancer in people.”

Epigenetic changes

To determine how the genes that are activated in breastfeeding women differ from those not breastfeeding, researchers isolated breast cells from milk donated from nine women who had been breastfeeding for less than a year and carried out a genetic analysis. They compared these to cells from tissue donated by seven women having aesthetic breast reduction surgery.

A form of genetic analysis called single-cell RNA sequencingTrusted Source showed genes that increase their expression during lactation related to fatty acid metabolism and storage, zinc transport, and secretion and immune response.

They also identified two distinct cell populations responsible for making breast milk in lactating women.

This differs from previous research showing just one type of cell in mice. Researchers were surprised to find that one of these groups of cells had high levels of expression of genes responsible for immune response not previously associated with human breast cells.

This finding alone reframed the question of why breast cells were found in human milk at all. Researchers suggested they could serve a role in helping the breastfed infant’s immune system be ‘trained’.

“I believe that by studying human milk cells, we will be able to answer some of the most fundamental questions around mammary gland function such as: how is milk produced? Why do some women struggle to make milk? and what strategies can be employed to improve breastfeeding outcomes for women?” says Dr. Alecia-Jane Twigger from the Wellcome-MRC Cambridge Stem Cell Institute, who led the study.

Insight into breast cancer origins

Researchers then performed further analyses to determine the origin of these cells, and researchers concluded they had differentiated from luminal progenitor cells as they had similar genetic profiles. Researchers concluded that determining the exact differentiation pathway would involve sampling cells or tissues as they differentiated in pregnant women, as lactation starts during pregnancy and then production increases when the placenta detaches from the womb after childbirth.

Luminal progenitor cells are significant to researchers as they are thought to be the cells in which cancerous mutations first originate.

Lead author Dr. Walid Khaled from the Wellcome-MRC Cambridge Stem Cell Institute said: “We’re not saying that the cells [found in breastmilk] themselves are going to go and give rise to cancer because that’s not true […] But because they do resemble the population of cells known as luminal progenitors, and probably are daughters of luminal progenitors, and have characteristics of luminal progenitors, that all of a sudden enables us to do studies on these cells with a lot of ease.”

Accessing donated breast milk had proved easy as many donors were willing, he said. Though the number of women contributing to this study was small, Dr. Khaled suggested that looking at changes in the breast following subsequent pregnancies using cells isolated from breastmilk could provide further insight into women’s health.

“You could imagine collecting a milk sample from a first pregnancy, and then once every now and then down the line from a second or third pregnancy. Then all of a sudden, you’ve got a window on how the breast has changed over that time, right? So I think that could potentially be really exciting.”

Source: Medical News Today

The nocebo effect: Can we think ourselves unwell?

 Almost everyone has heard of the placebo effect — when people experience beneficial effects from an inert drug. But few are aware of its flip side, the “nocebo effect.” Here, individuals taking a drug, whether placebo or not, experience unwanted, negative effects. Medical News Today spoke to experts in the field to investigate the basis of the nocebo effect and find out what might be done to minimize its impact on treatments and trials.

All drug trials must have a control group. People in this group receive an inert substance, also known as a placebo — a “fake” drug that does not contain an active ingredient.

If the trial is testing a specific pill, the control group will receive a pill that looks identical but does not contain an active ingredient. If testing a vaccine, the control group will receive a placebo injection.

However, there is a curious phenomenon whereby people taking placebos sometimes notice changes consistent with what they expect to happen.

Therefore, many will notice an improvement in symptoms — the so-called placebo effect. Others, however, will notice side effects that might be expected from the drug being trialed, and they may be unpleasant.

The term derives from the Latin word “nocere,” meaning “to harm,” and was first used to describe adverse effects caused by a placebo.

One study defined the nocebo effect as “unpleasant or adverse outcomes triggered by the treatment context, beyond any inherent pharmacological effects of the treatment itself.”

So the mere act of taking a tablet or having an injection might cause side effects, which are not due to any drug it contains. And it can happen to those on prescribed medication, not just in trials.

Cause of the nocebo effect

If the medication itself is not responsible for the side effects, why do they happen? The need for medical professionals to gain informed consentTrusted Source might go some way to explaining the nocebo effect.

People undergoing medical treatment must give informed consent for that treatment. To gain informed consent from a patient or trial participant, physicians have to explain the risks and benefits of the treatment in detail, including possible side effects. 

Older researchTrusted Source has suggested that when participants in a trial are told about side effects, they are likely to experience them whether they are taking the active drug or not.

So, can negative expectations produce negative outcomes? According to Chambers, this could be the case: “While it’s such a complex mix of things […] on the basic level, it’s having negative side effects because you have been told there might be negative side effects.”

Dr. Fabrizio Benedetti, professor of neuroscience at the University of Turin Medical School, Italy, who has published widely on the nocebo effect, agreed, noting that “[m]any adverse events may be attributable to nocebo effects and not so much to the drug itself.”

A recent studyTrusted Source of COVID-19 vaccination trials illustrates this. Researchers who analyzed data from 12 trials found that 35% of people given placebo injections experienced systemic effects — effects experienced in areas of the body other than the treatment site, such as headache and fatigue — following the first dose. 

This was compared with 46% of those given the real vaccine. Therefore, the authors of this study suggest that some 76% of adverse effects reported by those given the real vaccine were nocebo effects. In other words, they were not caused by the vaccine but by participants’ expectations.

Dr. Benedetti was unsurprised by these findings: “It has long been known that nocebo effects occur in many conditions, such as pain and Parkinson’s disease. Therefore, it is not surprising that they also take place in COVID-19 vaccination. If you expect a negative outcome, you can get it.”

Physical or mental causes?

These symptoms experienced are undoubtedly real, so if they are not due to active treatment, what might be the cause? Experts have attributed the nocebo effect to both psychological and neurobiological causesTrusted Source.

Dr. David A. Merrill, adult and geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in Santa Monica, CA, explained:

The psychology may be that negative expectations are fulfilled. If a patient hears that a treatment may cause drowsiness, and then feels drowsy, they will blame that sleepiness on the treatment.

In addition, people who have negative expectations of side effects may be more aware of symptoms and, therefore, more likely to report them.

And studiesTrusted Source have found that those who experience anxiety and depression may also be more likely to experience the nocebo effect.

Conditioning and past experience

Another explanation may lie in conditioning. The color of tablets is a case in point. A 1996 studyTrusted Source found that people associate red, yellow, or orange tablets with stimulant effects and blue or green tablets with sedative effects.

The researchers gave otherwise identical blue tablets to one group and pink to the other. The group taking the blue tablets reported more drowsiness.

And those who have experienced adverse drug effects in the past are more likely to report them after a new treatment.

One part of the nocebo effect that is a result of neurobiology is nocebo hyperalgesiaTrusted Source, where the expectation of pain increases the pain experienced.

When a person anticipates pain, they release cholecystokininTrusted Source, which allows pain transmission. If that anticipation and anxiety can be reduced, the pain will also be reduced.

Dr. Merrill explained how this happens: “Sensations can be amplified by our brain in feedback loops triggered by fear, which results in amplification of pain and other symptoms. This does not mean the pain is not real, but rather that the pain is primarily signaling fear rather than damage.”

Effect on treatment

The real risk with the nocebo effect is when it affects treatments or drug trials. If a person attributes negative side effects to an effective treatment, they might stop that treatment, losing the benefits along with the side effects. Over-reporting of side effects in a drug trial may mean that the drug does not get licensed.

This can have a real impact on health outcomes, as Lee Chambers outlined: “You don’t want someone to discontinue something that’s beneficial because of these negative effects that they feel they are having because of it. It [the nocebo effect] can increase those reported side effects… and lead to negative health outcomes.”

Some studiesTrusted Source have suggested that reducing information about side effects might reduce the nocebo effect, but there are ethical problems. When asked whether he thought withholding such information could be justified, Dr. Benedetti was clear:

Source: Medical News Today

A novel protein therapy for efficient skin wound healing

 A protein named Agrin has been discovered to promote wound healing and repair, when it is triggered after skin tissue is injured. These findings could pave the way for the development of Agrin protein therapy to accelerate skin tissue healing for chronic wounds from diabetes or burns. The research, led by A*STAR's Institute of Molecular and Cell Biology (IMCB), was published in the journal Nature Communications on 3 November 2021.

One in 20 Singaporeans is afflicted with chronic wound conditions. Complications in the healing of chronic wounds are prevalent in patients suffering from diabetes or burn injuries, and are a leading cause of amputation and decreased emotional wellbeing for patients. During injury, a major chunk of extracellular matrix (ECM) -- which helps to rebuild tissue -- is lost, therefore delaying wound healing. As such, the timely replenishment of key ECM proteins may accelerate wound healing.

In this study, researchers have shown that timely induction or exogenous supplementation of Agrin, an ECM protein, may promote accelerated healing of injured skin tissues. Using both human and pre-clinical models, they found that physical injury to the skin tissue enhanced the expression of Agrin, which preserves the mechanical architecture of injured skin layers by repairing the skin tissue.

The IMCB team in collaboration with the Mechanobiology Institute, National University of Singapore also discovered that a recombinant fragment of Agrin that can be easily produced, sAgrin, may serve as a bio-additive material to improve healing when applied as a topical hydrogel to the injured skin. These findings would advance the development of Agrin-based bio-scaffolds that could offer accelerated skin tissue healing by restoring the damaged tissue.

"We found that in our preclinical wound healing models, Agrin protein therapy offers accelerated healing, compared to collagen gels that are in the market. Besides healing wounds at a faster pace, Agrin therapy preserves the wound microenvironment that enforces better repair mechanisms than existing controls used in the study. The findings offer the potential for developing Agrin-based wound healing biomaterials that could help patients with chronic wounds," said Dr Sayan Chakraborty, Senior Research Scientist at A*STAR's IMCB and lead researcher of the study.

"Recent studies from various labs in the scientific community have implicated a role of Agrin in repair and regeneration of diverse tissues and organs. This study may offer a novel approach for regenerative medicine beyond conventional chronic wound treatments and improve health outcomes," said Professor Wanjin Hong, Executive Director of IMCB and senior corresponding author of the study.

Moving forward, the research team plans to extend testing of sAgrin therapy on pre-clinical wound healing models to improve the efficacy of the study, as well as to develop bioprinted scaffolds with Agrin that could help to repair damaged tissue.

Source:ScienceDaily

Can we go from scarface to scarless?

 Although human skin heals from injuries and wounds, many of us have scars that are left behind. Scar formation happens in adult mammals because skin regeneration does not fully occur. This poses a challenge to physicians who wish to conduct surgeries without scars appearing afterwards. In a newly published article in Biomedicines, a team led by researchers at the University of Tsukuba investigated the use of the adult newt, Cynops pyrrhogaster, as a model system for studying scarless wound healing for technology development in surgical and cosmetic medicine.

After an injury occurs, the epidermis, which is the outer layer of the skin, can grow and migrate to fill in the wound. This is known as re-epithelialization. Although this takes place, the original skin color and texture is sometimes not retained, leading to the appearance of what we know as a scar. Processes called granulation and dermal fibrosis underpin scar formation, making them a focus for scientists aiming to minimize scarring following clinical procedures. Amphibians have been used as animal models for studying this, because they do not scar prior to metamorphosis. However, it is not clear what happens to fully mature amphibian skin.

"We chose to examine the adult Japanese fire-bellied newt, which is a type of salamander that is well understood on the genetic level," explains Dr. Tatsuyuki Ishii, lead author of the study. "We know adult newts are capable of complicated tissue, organ, and limb regeneration. Despite that, their ability to regenerate skin has not been scientifically demonstrated."

The team excised a small piece of skin from various body parts of adult newts, including the head, trunk, limbs, and abdomen. They periodically observed the skin healing and regeneration progression for up to two years, making note of re-epithelialization and dermal fibrosis, as well as recovery of texture, appendage, and color.

"Interestingly, we found that the adult newts could successfully and fully regenerate their skin at each part of the body that we examined," describes Professor Chikafumi Chiba, senior author. "Re-epithelialization occurred at all locations, while no dermal fibrosis was observed at all."

However, the original color pattern of the dorsal-lateral and ventral skin was not restored. Because humans do not have such color patterns, the researchers believed this to be a newt-specific issue. Thus, they concluded that Cynops pyrrhogaster could be a perfect model system for investigating skin regeneration and scar formation in humans.

The team also further studied skin regeneration in these newts at the morphological and molecular level. The wounds tended to heal within only a few days, while skin regeneration took up to two years to complete. Inflammatory gene markers were only briefly expressed during wound healing.

"Dermal fibrosis is often characterized by prolonged inflammation at the wound site," explains Dr. Ishii. "Scar-free skin occurred in the newts through rapid re-epithelialization and skipping of granulation and dermal fibrosis."

Overall, these findings will be crucial for future studies in humans focusing on efforts to prevent scarring in human skin following various medical procedures.

Source: Science Daily

Antifreeze cream prevents frostbite injuries to skin, study suggests

 Skiers, hikers, soldiers and others exposed to extreme cold temperatures can experience frostbite -- a painful injury that occurs when ice crystals form in the skin. Many extremely cold areas are also remote, and delays in frostbite treatment can result in severe wounds, scarring and even limb amputation. Now, researchers reporting in ACS Applied Biomaterials have developed a cream that prevents frostbite injuries in mice when applied to the skin 15 minutes before severe cold exposure.

Frostbite not only kills skin cells, but can also harm deeper tissues like muscle and bone, sometimes causing secondary infections and permanent nerve damage. Common therapies, such as rapid rewarming of the affected limb, aim to reverse tissue freezing, but by the time of treatment, many cells have already died. Recently, scientists have developed frostbite prevention strategies, such as electric heaters sewn into clothing or transgenic antifreeze proteins, but such approaches are often costly, impractical or have safety concerns. Therefore, Munia Ganguli and colleagues wanted to test the frostbite prevention properties of a combination of synthetic molecules commonly used in labs to cryopreserve cells. Dimethyl sulfoxide (DMSO) keeps ice crystals from forming inside cells, whereas poly(vinyl alcohol) (PVA) prevents ice crystals in the spaces between cells, which can damage membranes.

The researchers first tested the ability of different amounts of DMSO and PVA, alone or in combination, to prevent the death of cultured cells in a dish that were exposed to a freezing temperature. They found that 2% DMSO combined with 1.6 mg/mL PVA yielded the highest cell survival (about 80%), while protecting the cell membrane and cytoskeleton. This combination, which the researchers called SynAFP, also allowed cells to divide and express proteins more normally after cold stress. Then, the team mixed SynAFP with a commercial aloe vera cream and applied it to the skin of mice 15 minutes before a cold challenge. The cream reduced frostbite wound size, tissue damage and inflammation, and sped healing, compared with no treatment. The cream did not prevent frostbite when applied 30 minutes or more before the cold challenge; however, multiple applications did not damage skin. The effects of the antifreeze cream in people, and how frequently it needs to be reapplied, must still be determined, the researchers say.

The authors acknowledge funding from the Defence Research and Development Organisation, the Department of Biotechnology Junior Research Fellowship and the Council of Scientific & Industrial Research (CSIR).

Source: ScienceDaily

What the rise of oxygen on early Earth tells us about life on other planets

 When did the Earth reach oxygen levels sufficient to support animal life? Researchers from McGill University have discovered that a rise in oxygen levels occurred in step with the evolution and expansion of complex, eukaryotic ecosystems. Their findings represent the strongest evidence to date that extremely low oxygen levels exerted an important limitation on evolution for billions of years.

"Until now, there was a critical gap in our understanding of environmental drivers in early evolution. The early Earth was marked by low levels of oxygen, till surface oxygen levels rose to be sufficient for animal life. But projections for when this rise occurred varied by over a billion years -- possibly even well before animals had evolved," says Maxwell Lechte, a postdoctoral researcher in the Department of Earth and Planetary Sciences under the supervision of Galen Halverson at McGill University.

Ironstones provide insights into early life

To find answers, the researchers examined iron-rich sedimentary rocks from around the world deposited in ancient coastal environments. In analyzing the chemistry of the iron in these rocks, the researchers were able to estimate the amount of oxygen present when the rocks formed, and the impact it would have had on early life like eukaryotic microorganisms -- the precursors to modern animals.

"These ironstones offer insights into the oxygen levels of shallow marine environments, where life was evolving. The ancient ironstone record indicates around less than 1 % of modern oxygen levels, which would have had an immense impact on ecological complexity," says Changle Wang, a researcher at the Chinese Academy of Sciences who co-led the study with Lechte.

"These low oxygen conditions persisted until about 800 million years ago, right when we first start to see evidence of the rise of complex ecosystems in the rock record. So if complex eukaryotes were around before then, their habitats would have been restricted by low oxygen," says Lechte.

Earth remains the only place in the universe known to harbor life. Today, Earth's atmosphere and oceans are rich with oxygen, but this wasn't always the case. The oxygenation of the Earth's ocean and atmosphere was the result of photosynthesis, a process used by plants and other organisms to convert light into energy -- releasing oxygen into the atmosphere and creating the necessary conditions for respiration and animal life.

Searching for signs of life beyond our solar system

According to the researchers, the new findings suggests that Earth's atmosphere was capable of maintaining low levels of atmospheric oxygen for billions of years. This has important implications for exploration of signs of life beyond our solar system, because searching for traces of atmospheric oxygen is one way to look for evidence of past or present life on another planet -- or what scientists call a biosignature.

Scientists use Earth's history to gauge the oxygen levels under which terrestrial planets can stabilize. If terrestrial planets can stabilize at low atmospheric oxygen levels, as suggested by the findings, the best chance for oxygen detection will be searching for its photochemical byproduct ozone, say the researchers.

"Ozone strongly absorbs ultraviolet light, making ozone detection possible even at low atmospheric oxygen levels. This work stresses that ultraviolet detection in space-based telescopes will significantly increase our chances of finding likely signs of life on planets outside our solar system," says Noah Planavsky, a biogeochemist at Yale University.

More geochemical studies of rocks from this time period will allow scientists to paint a clearer picture of the evolution of oxygen levels during this time, and better understand the feedbacks on the global oxygen cycle, say the researchers.

Source: ScienceDaily

Extreme heat is the 'new normal' for the ocean

 New Monterey Bay Aquarium-led research reveals excessively warm ocean temperatures driven by climate change are the new normal. The study, published today by PLOS Climate, establishes that more than half of the ocean surface has exceeded a historical heat extreme threshold on a regular basis since 2014.

And it is these heat extremes, researchers say, that increase the risk of collapse for crucial marine ecosystems, including coral reefs, seagrass meadows, and kelp forests -- altering their structure and function, and threatening their capacity to continue to provide life-sustaining services to human communities.

Researchers conducted the study by mapping 150 years of sea surface temperatures to determine a fixed historical benchmark for marine heat extremes. The scientists then looked at how often and how much of the ocean surpassed this point. The first year in which more than half of the ocean experienced heat extremes was 2014. The trend continued in subsequent years, reaching 57 percent of the ocean in 2019, the last year measured in the study. Using this benchmark, just two percent of the ocean surface was experiencing extremely warm temperatures at the end of the 19th century.

"Climate change is not a future event," said Dr. Kyle Van Houtan, who headed the research team during his tenure as chief scientist for the aquarium. "The reality is that it's been affecting us for a while. Our research shows that for the last seven years more than half of the ocean has experienced extreme heat."

"These dramatic changes we've recorded in the ocean are yet another piece of evidence that should be a wake-up call to act on climate change," he added." We are experiencing it now, and it is speeding up."

The study grew from separate research into the history of kelp forest changes throughout California. Van Houtan and team discovered that sea surface heat extremes, which are key stressors for canopy kelps, needed to be quantified and mapped along the California coast throughout the last century. The researchers then decided to expand the investigation beyond California to better understand the long-term frequency and location of extreme marine heat across the global ocean surface.

Using historic records, aquarium scientists first determined the average temperatures for the ocean's surface over the period spanning 1870 to 1919. Then they identified the most dramatic ocean warming that occurred during that period -- the top two percent of temperature increases -- and defined that as "extreme heat." The team then mapped the extremes over time, examining whether they occur regularly or are becoming more frequent.

"Today, the majority of the ocean's surface has warmed to temperatures that only a century ago occurred as rare, once-in-50-year extreme warming events," Van Houtan said.

The researchers say the new normal of extreme heat across the majority of the ocean's surface is further evidence for the urgent need to drastically reduce emissions from the burning of fossil fuels, which are the driver of climate change.

"When marine ecosystems near the tropics experience intolerably high temperatures, key organisms such as corals, seagrass meadows, or kelp forests can collapse," Van Houtan said. "Altering ecosystem structure and function threatens their capacity to provide life-sustaining services to human communities like supporting healthy and sustainable fisheries, buffering low-lying coastal regions from extreme weather events, and serving as a carbon sink to store the excess carbon put in the atmosphere from human-generated greenhouse emissions."

Story Source: ScienceDaily