Your mouth is a magician. Bite the inside of your cheek, and the wound may vanish without a trace in a couple of days. A preclinical study co-led by Cedars-Sinai, Stanford Medicine and the University of California, San Francisco (UCSF), has discovered one secret of this disappearing act. The findings, if confirmed in humans, could one day lead to treatments that enable rapid, scarless recovery from skin wounds on other parts of the body.
“Our research began with two questions: Why does your mouth heal so much better than your skin?” said Ophir Klein MD, PhD, co-corresponding author of the study. “And if we figure that out, can we use that information therapeutically?”
The need for therapies is clear. Wounds to the lining of the mouth typically disappear in one to three days. But skin wounds may take nearly three times as long to heal and can leave unsightly scars.
“Unfortunately, current treatments do not adequately resolve or prevent scarring because we do not fully understand the mechanism,” Klein said. “Our research helps fill in that knowledge gap.”
In the study, investigators analysed tissue samples from the lining of the mouth, known as the oral mucosa, and the facial skin of laboratory mice. In the oral mucosa, they found a signaling pathway between cells, involving a protein called GAS6 and an enzyme called AXL, which blocks a different cellular pathway, known as FAK, that promotes scarring.
When the investigators inhibited the AXL enzyme in the laboratory mice, the oral mucosa wounds’ healing worsened, making them more like skin wounds. When AXL was stimulated in the skin wounds, they healed much like oral mucosa wounds, regenerating tissue more efficiently.
“This data shows that the GAS6-AXL pathway is potentially important for scarless healing in the mouth and that manipulating it may help reduce skin scars as well,” Klein said.
The next steps are to determine how these preclinical findings apply to humans and to develop therapies to improve healing of skin wounds, according to Michael Longaker, MD, Professor in the School of Medicine at Stanford University, and the study’s co-corresponding author.
“Further clinical studies should be performed to assess the nature of the relationship between AXL and scarring in humans,” Longaker said.
A woman with Systemic Lupus Erythematosus. Source: Wikimedia CC0
Chronic inflammation occurs when the immune system is stuck in attack mode, sending cell after cell to defend and repair the body for months or even years. Diseases associated with chronic inflammation, like arthritis or cancer or autoimmune disorders, weigh heavily on human health – and their incidence is expected to rise. A new study by investigators from Mass General Brigham identified a protein called WSTF that could be targeted to block chronic inflammation. Crucially, this strategy would not interfere with acute inflammation, allowing the immune system to continue responding appropriately to short-term threats, such as infection by a pathogen. Results are published in Nature.
“Chronic inflammatory diseases cause a great deal of suffering and death, but we still have much to learn about what drives chronic inflammation and how to treat it,” said senior author Zhixun Dou, PhD, of the Center for Regenerative Medicine and Krantz Family Center for Cancer Research at Massachusetts General Hospital. “Our findings help us separate chronic and acute inflammation, as well as identify a new target for stopping chronic inflammation that results from aging and disease.”
Using chronically inflamed human cells, the researchers found that WSTF interacts with other proteins inside cell nuclei, which prompts its excretion and degradation. Since WSTF is responsible for concealing pro-inflammatory genes, this nucleus-eviction reveals those genes and, in turn, amplifies inflammation. They confirmed that WSTF loss could promote inflammation in mouse models of aging and cancer. They also found, using human cells, that WSTF loss only occurred in chronic inflammation, not acute. Using these findings, the researchers designed a WSTF-restoring therapeutic to suppress chronic inflammation and observed preliminary success in mouse models of aging, metabolic dysfunction-associated steatohepatitis (MASH), and osteoarthritis.
The researchers went further to examine tissue samples from patients with MASH or osteoarthritis. They found that WSTF is lost in the livers of patients with MASH, but not in the livers of healthy donors. Using cells from the knees of osteoarthritis patients undergoing joint replacement surgery, they showed that WSTF-restoring therapeutic reduces chronic inflammation from the inflamed knee cells. These findings highlight the potential of developing new treatments targeting WSTF to combat chronic inflammatory diseases.
Further research is needed to validate the therapeutic potential of WSTF restoration in broader settings and to develop specific strategies to target WSTF. Additionally, the findings suggest other similar proteins may be involved in chronic inflammation, opening a promising new avenue for studying and treating inflammation in the future.
COVID-19 has largely dropped out of the headlines, but the virus that causes it is still circulating. We ask what we should know about a new variant of SARS-CoV-2, the state of the COVID-19 pandemic in 2025, and the lack of access to updated vaccines in South Africa.
In the leafy Johannesburg suburb of Sandringham, the National Institute for Communicable Diseases (NICD) bears a deceptive facade. Do not be fooled by its sleepy campus, clustered face brick buildings and shade-cloth parking, this government facility is home to state-of-the-art biosafety laboratories and some of South Africa’s top virologists, microbiologists and epidemiologists. Here, 71 scientists are tasked daily with laboratory-based disease surveillance to protect the country from pathogen outbreak events.
On 5 March 2020, then health minister Dr Zweli Mkhize announced South Africa’s first COVID‑19 infection at an NICD press briefing. At the time, the NICD was an obscure acronym for many – but that quickly changed as the institution became central to the country’s pandemic response.
While the COVID-19 pandemic may have waned, the NICD hasn’t stopped monitoring.
That is because there remains a global public health risk associated with COVID-19. The World Health Organization (WHO) states: “There has been evidence of decreasing impact on human health throughout 2023 and 2024 compared to 2020-2023, driven mainly by: 1) high levels of population immunity, achieved through infection, vaccination, or both; 2) similar virulence of currently circulating JN.1 sublineages of the SARS-CoV-2 virus as compared with previously circulating Omicron sublineages; and 3) the availability of diagnostic tests and improved clinical case management. SARS-CoV-2 circulation nevertheless continues at considerable levels in many areas, as indicated in regional trends, without any established seasonality and with unpredictable evolutionary patterns.”
Thus, while SARS-CoV-2 is still circulating, it is clearly not making remotely as many people ill or claiming nearly as many lives as it did four years ago. Asked about this, Foster Mohale, spokesperson for the National Department of Health, says “there are no reports of people getting severely sick and dying due to COVID-19 in South Africa at the current moment”.
‘Variant under monitoring’
As SARS-CoV-2 circulates, it continues to mutate. The WHO recently designated variant NB.1.8.1 as a new variant under monitoring. There is however no reason for alarm. Professor Anne von Gottberg, laboratory head at the NICD’s Centre for Respiratory Diseases and Meningitis, tells Spotlight that NB.1.8.1 is not a cause for panic, particularly not in South Africa.
Von Gottberg says no cases of the new variant has been detected in South Africa. She refers to her unit’s latest surveillance of respiratory pathogens report for the week of 2 to 8 June 2025. It states that out of 189 samples tested, 41 (21.7%) cases were influenza, another 41 (21.7%) cases were respiratory syncytial virus (RSV), and three (1.6%) cases were earlier strains of SARS-CoV-2.
These figures suggest much greater circulation of influenza and RSV in South Africa than SARS-CoV-2. Over the past six months, 3 258 samples were tested, revealing 349 (10.7%) cases of influenza, 530 (16.3%) cases of RSV, and 106 (3.3%) cases of SARS-CoV-2. Since most people who become sick because of these viruses are not tested, these figures do not paint the whole picture of what is happening in the country.
As of 23 May 2025, the WHO considered the public health risk of NB.1.8.1 to be “low at the global level”, with 518 iterations of the variant submitted from 22 countries, mainly around Asia and the Pacific islands.
The WHO report states: “NB.1.8.1 exhibits only marginal additional immune evasion over LP.8.1 [first detected in July 2024]. While there are reported increases in cases and hospitalisations in some of the WPR [Western Pacific Region] countries, which has the highest proportion of NB.1.8.1, there are no reports to suggest that the associated disease severity is higher as compared to other circulating variants. The available evidence on NB.1.8.1 does not suggest additional public health risks relative to the other currently circulating Omicron descendent lineages.”
Combating misinformation
Von Gottberg says that the NICD plays a critical public health communication role in combating misinformation and warns against alarmist and inaccurate online depictions of NB.1.8.1, the Omicron-descendent lineage dubbed “Nimbus” by some commentators.
“There’s fake news about NB.1.8.1 going around on social media,” she says. “For example, supposed symptoms. I have been trying to look for articles and have not seen anything from [reliable sources],” she says. “In fact, there is no information about whether there are any differences in symptoms, because there are so few cases and it is not causing more severe disease.”
Von Gottberg implores members of the public to check information sources. “We try hard – and the Department of Health does the same – to put media releases out so that accurate information is shared. What we ask is that all our clients, the public, verify information before they start retweeting or resending.”
COVID-19 vaccines in South Africa
The WHO recommends that countries ensure continued equitable access to and uptake of COVID-19 vaccines. They also note that the currently approved COVID-19 vaccines are expected to remain effective against the new variant. But contrary to WHO advice, newer COVID-19 vaccines are not available in South Africa and continued access to older vaccination seems to have ceased. When Spotlight called two branches of two different major pharmacy retailers in Cape Town asking for available COVID-19 vaccines, the answer at both was that they have none.
Several recently approved COVID-19 vaccines are being used in other countries but are not available in South Africa. These include Moderna’s updated mRNA boosters, approved in the United States and parts of Europe, Novavax’s Nuvaxovid vaccine, approved in the United States, and Arcturus Therapeutics’s self-amplifying mRNA vaccine Zapomeran, approved in Europe. Self-amplifying mRNA vaccines has the additional capacity to induce longer lasting immune responses by replicating the spike-proteins of SARS-CoV-2.
None of these vaccines are under review for registration in South Africa, according to the South African Health Products Regulatory Authority (SAHPRA). Vaccines may not be made available in the country without the green light from SAHPRA. “It may be advisable to contact the owners of the vaccines to obtain clarity on whether they intend to submit for registration,” says SAHPRA spokesperson Yuven Gounden.
Spotlight on Friday sent questions to Moderna, Novavax, and Arcturus, asking whether they plan to submit their vaccines for registration with SAHPRA, and if not, why not. None of the companies responded by the time of publication.
Von Gottberg explains that vaccines can only become available in South Africa if their manufacturers submit them to SAHPRA for approval. “So, if a vaccine provider, a vaccine manufacturer, does not want to sell in our country because they do not see it as a lucrative market, they may not even put it forward for regulation so that it can be made available.”
Professor of Vaccinology at the University of the Witwatersrand, Shabir Madhi, says the major concern with the lack of licensed SARS-CoV-2 vaccines in South Africa is that “high-risk individuals remain susceptible to severe COVID-19, as there is waning of immunity”.
“High-risk individuals should receive a booster dose every 6-12 months, preferably with the vaccine that is updated against current or most recent variants,” he says.
Von Gottberg has similar concerns. “My hope as a public health professional is that these vaccine manufacturers take us seriously as a market in South Africa and in Africa, very importantly, and put these vaccines and products through our regulatory authorities so that they can be made available both in the public and in the private sector for all individuals who are at risk and should be receiving these vaccines,” she says.
Gounden notes that should a public health need arise, “SAHPRA is ready to respond in terms of emergency use approval.”
Concerns over vaccine expert dismissals in the United States
Earlier this month in the United States, Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. fired all 17 members of the Advisory Committee on Immunisation Practices (ACIP) – an expert body responsible for recommending vaccines for 60 years. He then appointed eight new members, some known for vaccine skepticism.
Commenting on this, Von Gottberg says: “I am hoping there will be those who will think about what he [Kennedy] is doing and question it. It is an unusual situation in the United States, you cannot call it business as usual.”
In an article published in the Journal of the American Medical Association, former ACIP members voice grave concerns over the dismissals. “Vaccines are one of the greatest global public health achievements. Vaccine recommendations have been critical to the global eradication of smallpox and the elimination of polio, measles, rubella, and congenital rubella syndrome in the US. They have also dramatically decreased cases of hepatitis, meningitis, mumps, pertussis (whooping cough), pneumonia, tetanus, and varicella (chickenpox), and prevented cancers caused by hepatitis B virus and human papilloma viruses. Recent scientific advancements enabled the accelerated development, production, and evaluation of COVID-19 vaccines…,” they write.
The article also questioned the announcement by Kennedy Jr. on X that he had signed a directive to withdraw the recommendation for COVID-19 vaccination in healthy children and healthy pregnant people.
“[R]ecent changes to COVID-19 vaccine policy, made directly by the HHS secretary and released on social media, appear to have bypassed the standard, transparent and evidence-based review process. Such actions reflect a troubling dis-regard for the scientific integrity that has historically guided US immunisation strategy,” the authors warn.
Von Gottberg adds: “We hope that this anti-vax, the denialism of vaccines and the good they do, won’t come to South Africa.”
In addition, she cautions public healthcare professionals to take heed of this discourse. “We must take seriously that people have questions, and that they want to see us doing things correctly, transparently, always telling people of our conflicts of interest, being very upfront when things are controversial, when it’s difficult to make decisions,” she says. “So I think what this teaches us is not to be complacent in the way we talk and write about vaccines, discuss vaccines, and we must take our clients, the public out there seriously and hear their voices, listen to their questions.”
What do the brains of newborns and patients with Alzheimer’s disease have in common? Researchers from the University of Gothenburg, led by first author Fernando Gonzalez-Ortiz and senior author Professor Kaj Blennow, recently reported that both newborns and Alzheimer’s patients have elevated blood levels of a protein called phosphorylated tau, specifically a form called p-tau217.
While this protein has been largely used as a diagnostic test for Alzheimer’s disease, with an increase in p-tau217 blood levels proposed to be driven by another process, namely aggregation of b-amyloid protein into amyloid plaques. Newborns (for natural reasons) do not have this type of pathological change, so interestingly, in newborns increased plasma p-tau217 seems to reflect a completely different – and entirely healthy – mechanism.
In a large international study that involved Sweden, Spain and Australia, researchers analyzed blood samples from over 400 individuals, including healthy newborns, premature infants, young adults, elderly adults, and people diagnosed with Alzheimer’s disease. They found that newborn babies had the highest levels of p-tau217 – even higher than those found in people with Alzheimer’s. These levels were particularly elevated in premature babies and started to decrease over the first few months of life, eventually settling to adult levels.
First time in the blood of newborns
Previous research, largely based on animal models, had hinted at the role of phosphorylated tau in early brain development. This is the first time scientists have directly measured p-tau217 concentrations in the blood of human newborns, opening the door to a much clearer understanding of its developmental role.
But here’s where it gets fascinating, while in Alzheimer’s disease p-tau217 is associated with tau aggregation into harmful clumps called tangles, believed to cause the breakdown of brain cells and subsequent cognitive decline. In contrast, in newborns this surge in tau appears to support healthy brain development, helping neurons grow and to form new connections with other neurons, thereby shaping the structure of the young brain.
The study also revealed that in both healthy and premature babies, p-tau217 levels were closely linked to how early they were born. The earlier the birth, the higher the levels of this protein, suggesting a role in supporting rapid brain growth under challenging developmental conditions.
Potential roadmap for new treatments
What’s perhaps most compelling about these findings, published in the journal Brain Communications, is the hint that our brains may once have had built-in protection against the damaging effects of tau, so that newborns can tolerate, and even benefit from, high levels of phosphorylated tau without triggering the kinds of damage seen in Alzheimer’s.
“We believe that understanding how this natural protection works – and why we lose it as we age – could offer a roadmap for new treatments. If we can learn how the newborn brain keeps tau in check, we might one day mimic those processes to slow or stop Alzheimer’s in its tracks”, says Fernando Gonzalez-Ortiz.
So while an increase of p-tau217 is a danger signal in older brains, in newborns it might be a vital part of building one. The same molecule, two dramatically different roles – one building the brain, the other marking its decline.
Plasma p-tau217 has recently received FDA approval for use in diagnosing Alzheimer’s disease, making it an increasingly important tool in clinical settings. The authors emphasise
Source: the need to also understand the mechanism for the increase in p-tau217, especially for interpreting it as an outcome in clinical and epidemiological research and in drug development. This study indicate that amyloid plaques may not be the main driver of increases in p-tau217.
