Categories : General Interest Medical Research & TechnologyTags :

Researchers Spot Chimpanzees Using Medicinal Leaves to Perform First Aid

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Social grooming between two chimpanzees in the Budongo Forest. Photograph by Dr Elodie Freymann.

Researchers monitoring chimpanzee communities in the Budongo Forest, Uganda, noticed that individuals were helping each other with wound care and hygiene. Some of the chimpanzees even used fresh, chewed leaves from plants known for their traditional medicinal uses and bioactive properties to treat their own and their companions’ wounds. Remarkably, they helped individuals they were genetically related to and individuals they weren’t, despite the potential risk from being exposed to pathogens. Researchers believe these findings could help us understand the cognitive and social foundations of healthcare. 

Researchers studying chimpanzees in Budongo Forest, Uganda, have observed that these primates don’t just treat their own injuries, but care for others, too – information which could shed light on how our ancestors first began treating wounds and using medicines. Although chimpanzees elsewhere have been observed helping other community members with medical problems, the persistent presence of this behaviour in Budongo could suggest that medical care among chimpanzees is much more widespread than we realised, and not confined to care for close relatives.  

“Our research helps illuminate the evolutionary roots of human medicine and healthcare systems,” said Dr Elodie Freymann, research affiliate at the School of Anthropology and Museum Ethnography, Oxford University, first author of the article in Frontiers in Ecology and Evolution. “By documenting how chimpanzees identify and utilise medicinal plants and provide care to others, we gain insight into the cognitive and social foundations of human healthcare behaviours.” 

The researchers studied two communities of chimpanzees in the Budongo Forest – Sonso and Waibira. Like all chimpanzees, members of these communities are vulnerable to injuries, whether caused by fights, accidents, or snares set by humans. About 40% of all individuals in Sonso have been seen with snare injuries. 

The researchers spent four months observing each community, as well as drawing on video evidence from the Great Ape Dictionary database, logbooks containing decades of observational data, and a survey of other scientists who had witnessed chimpanzees treating illness or injury. Any plants chimpanzees were seen using for external care were identified; several turned out to have chemical properties which could improve wound healing and relevant traditional medicine uses. 

During their direct observational periods, the researchers recorded 12 injuries in Sonso, all of which were likely caused by within-group conflicts. In Waibira, five chimpanzees were injured – one female by a snare, and four males in fights. The researchers also identified more cases of care in Sonso than in Waibira. 

“This likely stems from several factors, including possible differences in social hierarchy stability or greater observation opportunities in the more thoroughly habituated Sonso community,” said Freymann. 

The researchers documented 41 cases of care overall: seven cases of care for others – prosocial care – and 34 cases of self-care. These cases often included several different care behaviours, which might be treating different aspects of a wound, or might reflect a chimpanzee’s personal preferences.  

“Chimpanzee wound care encompasses several techniques: direct wound licking, which removes debris and potentially applies antimicrobial compounds in saliva; finger licking followed by wound pressing; leaf-dabbing; and chewing plant materials and applying them directly to wounds,” said Freymann. “All chimpanzees mentioned in our tables showed recovery from wounds, though of course we don’t know what the outcome would have been had they not done anything about their injuries.  

“We also documented hygiene behaviours, including the cleaning of genitals with leaves after mating and wiping the anus with leaves after defecation – practices that may help prevent infections.” 

Of the seven instances of prosocial care, the researchers found four cases of wound treatment, two cases of snare removal assistance, and one case where a chimpanzee helped another with hygiene. Care wasn’t preferentially given by, or provided to, one sex or age group. On four occasions, care was given to genetically unrelated individuals.  

“These behaviours add to the evidence from other sites that chimpanzees appear to recognise need or suffering in others and take deliberate action to alleviate it, even when there’s no direct genetic advantage,” said Freymann. 

The researchers call for more research into the social and ecological contexts in which care takes place, and which individuals give and receive care. One possibility is that the high risk of injury and death which Budongo chimpanzees all face from snares could increase the likelihood that these chimpanzees care for each other’s wounds, but more data is needed to explore this.  

“Our study has a few methodological limitations,” cautioned Freymann. “The difference in habituation between the Sonso and Waibira communities creates an observation bias, particularly for rare behaviours like prosocial healthcare. While we documented plants used in healthcare contexts, further pharmacological analyses are needed to confirm their specific medicinal properties and efficacy. Also, the relative rarity of prosocial healthcare makes it challenging to identify patterns regarding when and why such care is provided or withheld. These limitations highlight directions for future research in this emerging field.” 

Source: Oxford University

Categories : NeurologyTags :

Hormone Supplementation in Rhesus Monkeys Points to Potential Autism Treatment

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Photo by Peter Burdon on Unsplash

For years, Florida Tech’s Catherine Talbot, assistant professor of psychology, has worked to understand the sociality of male rhesus monkeys and how low-social monkeys can serve as a model for humans with autism. Her most recent findings show that replenishing a deficient hormone, vasopressin, helped the monkeys become more social without increasing their aggression – a discovery that could change autism treatment.

Currently, the Centers for Disease Control and Prevention report that one in 36 children in the United States is affected by autism spectrum disorder (ASD). That’s an increase from one in 44 children reported in 2018. Two FDA-approved treatments currently exist, Talbot said, but they only address associated symptoms, not the root of ASD. The boost in both prevalence and awareness of the disorder prompts the following question: What is the cause?

Some rhesus monkeys are naturally low-social, meaning they demonstrate poor social cognitive skills, while others are highly social. Their individual variation in sociality is comparable to how human sociality varies, ranging from people we consider social butterflies to those who are not interested in social interactions, similar to some people diagnosed with ASD, Talbot said. Her goal has been to understand how variations in biology and behaviour influence social cognition.

In their paper published in the journal PNAS, Talbot and researchers with Stanford, the University of California, Davis and the California National Primate Research Center explored vasopressin, a hormone that is known to contribute to mammalian social behaviour, as a potential therapeutic treatment that may ultimately help people with autism better function in society. Previous work from this research group found that vasopressin levels are lower in their low-social rhesus monkey model, as well as in a select group of people with ASD.

Previous studies testing vasopressin in rodents found that increased hormone levels caused more aggression. As a result, researchers warned against administering vasopressin as treatment, Talbot said. However, she argued that in those studies, vasopressin induced aggression in contexts where aggression is the socially appropriate response, such as guarding mates in their home territory, so the hormone may promote species-typical behaviour.

She also noted that the previous studies tested vasopressin in “neurotypical” rodents, as opposed to animals with low-social tendencies.

“It may be that individuals with the lowest levels of vasopressin may benefit the most from it – that is the step forward toward precision medicine that we now need to study,” Talbot said.

In her latest paper, Talbot and her co-authors tested how low-social monkeys, with low vasopressin levels and high autistic-like trait burden, responded to vasopressin supplementation to make up for their natural deficiency. They administered the hormone through a nebulizer, which the monkeys could opt into. For a few minutes each week, the monkeys voluntarily held their face up to a nebulizer to receive their dose while sipping white grape juice – a favorite among the monkeys, Talbot said.

After administering the hormone and verifying that it increased vasopressin levels in the central nervous system, the researchers wanted to see how the monkeys responded to both affiliative and aggressive stimuli by showing them videos depicting these behaviors. They also compared their ability to recognize and remember new objects and faces, which is another important social skill.

They found that normally low-social monkeys do not respond to social communication and were better at recognizing and remembering objects compared to faces, similar to some humans diagnosed with ASD. When the monkeys were given vasopressin, they began reciprocating affiliative, pro-social behaviors, but not aggression. It also improved their facial recognition memory, making it equivalent to their recognition memory of objects.

In other words, vasopressin “rescued” low-social monkeys’ ability to respond prosocially to others and to remember new faces. The treatment was successful – vasopressin selectively improved the social cognition of these low-social monkeys.

“It was really exciting to see this come to fruition after pouring so much work into this project and overcoming so many challenges,” Talbot said of her findings.

One of Talbot’s co-authors has already begun translating this work to cohorts of autism patients. She expects more clinical trials to follow.

In the immediate future, Talbot is examining how other, more complex social cognitive abilities like theory of mind – the ability to take the perspective of another – may differ in low-social monkeys compared to more social monkeys and how this relates to their underlying biology. Beyond that, Talbot hopes that they can target young monkeys who are “at-risk” of developing social deficits related to autism for vasopressin treatment to see if early intervention might help change their developmental trajectory and eventually translate this therapy to targeted human trials. 

Source: Florida Tech

Categories : Uncategorized

A New LSD Analogue with Potential for Treating Schizophrenia

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A cortical neuron treated with JRT, a synthetic molecule similar to the psychedelic drug LSD. Drugs like JRT might enable new treatments for conditions such as schizophrenia, without the hallucinations and other side effects of psychedelics. (Photo credit: Lee E. Dunlap, Institute for Psychedelics and Neurotherapeutics, UC Davis)

University of California, Davis, researchers have developed a new, neuroplasticity-promoting drug closely related to LSD that harnesses the psychedelic’s therapeutic power with reduced hallucinogenic potential.

The research, published in PNAS, highlights the new drug’s potential as a treatment option for conditions like schizophrenia, where psychedelics are not prescribed for safety reasons. The compound also may be useful for treating other neuropsychiatric and neurodegenerative diseases characterised by synaptic loss and brain atrophy.

To design the drug, dubbed JRT, researchers flipped the position of just two atoms in LSD’s molecular structure. The chemical flip reduced JRT’s hallucinogenic potential while maintaining its neurotherapeutic properties, including its ability to spur neuronal growth and repair damaged neuronal connections that are often observed in the brains of those with neuropsychiatric and neurodegenerative diseases.

“Basically, what we did here is a tire rotation,” said corresponding author David E. Olson, director of the Institute for Psychedelics and Neurotherapeutics and a professor of chemistry, and biochemistry and molecular medicine at UC Davis. “By just transposing two atoms in LSD, we significantly improved JRT’s selectivity profile and reduced its hallucinogenic potential.”

JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia, without exacerbating behaviours and gene expression associated with psychosis.

“No one really wants to give a hallucinogenic molecule like LSD to a patient with schizophrenia,” said Olson, who is also co-founder and chief innovation officer of Delix Therapeutics, a company that aims to bring neuroplastogens to the market. “The development of JRT emphasises that we can use psychedelics like LSD as starting points to make better medicines. We may be able to create medications that can be used in patient populations where psychedelic use is precluded.”

Testing JRT’s potential

Olson said that it took his team nearly five years to complete the 12-step synthesis process to produce JRT. The molecule was named after Jeremy R. Tuck, a former graduate student in Olson’s laboratory, who was the first to synthesise it and is a co-first author of the study along with Lee E. Dunlap, another former graduate student in Olson’s laboratory.

Following JRT’s successful synthesis, the researchers conducted a battery of cellular and mouse assays that demonstrated the drug’s neuroplastic effects and improved safety profile relative to LSD.

Key findings included:

  • JRT and LSD have the exact same molecular weight and overall shape, but distinct pharmacological properties.
  • JRT is very potent and highly selective for binding to serotonin receptors, specifically 5-HT2A receptors, the activation of which are key to promoting cortical neuron growth.
  • JRT promoted neuroplasticity, or growth between cellular connections in the brain, leading to a 46% increase in dendritic spine density and an 18% increase in synapse density in the prefrontal cortex.
  • JRT did not produce hallucinogenic-like behaviors that are typically seen when mice are dosed with LSD.
  • JRT did not promote gene expression associated with schizophrenia. Such gene expression is typically amplified with LSD use.
  • JRT produced robust anti-depressant effects, with it being around 100-fold more potent than ketamine, the state-of-the-art fast-acting anti-depressant.
  • JRT promoted cognitive flexibility, successfully addressing deficits in reversal learning that are associated with schizophrenia.

“JRT has extremely high therapeutic potential. Right now, we are testing it in other disease models, improving its synthesis, and creating new analogues of JRT that might be even better,” Olson said.

A more effective treatment for schizophrenia

Olson emphasised JRT’s potential for treating the negative and cognitive symptoms of schizophrenia, as most current treatments produce limited effects on anhedonia — the inability to feel pleasure — and cognitive function. Clozapine is the one exception, but it has side effects, and is not first-line drug of choice for people with severe schizophrenia.

Olson and his team are currently testing JRT’s potential against other neurodegenerative and neuropsychiatric diseases.

Source: University of California – Davis

Categories : AntibioticsTags :

The Current Gonorrhoea Meds Might Stop Working – When Will Newer Ones Make it to SA?

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Neisseria gonorrhoeae Bacteria Scanning electron micrograph of Neisseria gonorrhoeae bacteria, which causes gonorrhea. Captured by the Research Technologies Branch (RTB) at the NIAID Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID. Photo by National Institute of Allergy and Infectious Diseases on Unsplash

By Catherine Tomlinson

Two new antibiotics offer hope for people with gonorrhoea that is resistant to currently available drugs. Yet, it might be years before the people who need these medicines can get them. Spotlight unpacks why these new antibiotics are important and what needs to happen before they can be used in South Africa.

Gonorrhoea is a sexually transmitted infection known for its ability to quickly mutate to evade the antibiotics used to treat it. Its symptoms include pain when urinating and genital discharge, but many people don’t notice any symptoms at all. If gonorrhoea is not treated, it can cause serious problems including infertility, chronic pain and complications in babies who risk developing infections that can cause eye damage and blindness.

Gonorrhoea treatment has been something of a cat-and-mouse game as the bacteria continuously developed resistance against the antibiotics used to treat it. From the 1990s to the early 2000s, the antibiotic ciprofloxacin was used to treat gonorrhoea in South Africa, sometimes combined with another one called doxycycline. But as high levels of ciprofloxacin resistance emerged, South Africa replaced this course of therapy with a regimen of cefixime and doxycycline. Gonorrhoea treatment was changed again in 2015, due to concerns regarding the emergence of cefixime-resistance.

Source: PowerPoint presentation on STI and antibiotic resistance by Professor Remco Peters.

The treatment regimen adopted in 2015 remains the standard of care in South Africa and much of the world today. It involves an intermuscular injection of ceftriaxone, combined with oral azithromycin pills. Although, some countries now recommend using high dose injectable ceftriaxone on its own, due to high levels of azithromycin resistance.

While most gonorrhoea cases are still treatable with ceftriaxone, the emergence of ceftriaxone-resistant gonorrhoea has been identified as a major global health threat.

“The last effective drug we have, ceftriaxone, already indicates increasing gonococcal resistance. Without new antibiotics, we will have no easy treatment options. This is a great concern that will have a major impact in disease control efforts,” warned the World Health Organization (WHO).

This is why two new antibiotics, zoliflodacin and gepotidacin, are considered such a big deal. They are the first new medicines developed for gonorrhoea in over 30 years. Both are in new classes of antibiotics, which is to say they attack the bacterium in a different way than previous medicines. Because of this, they have little cross resistance with existing treatments and therefore offer important treatment options for people for whom the old medicines no longer work.

How widespread is ceftriaxone-resistance in South Africa?

How urgently we need access to the new medicines in South Africa will depend largely on how many people here are resistant to ceftriaxone. Unfortunately, we don’t have a clear picture of drug-resistant gonorrhoea in the country.

South Africa introduced a syndromic management approach for sexually transmitted infections (STIs) in the mid-1990s, as recommended by the WHO. This means that people reporting STI symptoms at health facilities are treated according to their symptoms, rather than results of a lab test.

This approach to STIs helps to reduce the cost burden of laboratory diagnosis and allows for immediate treatment initiation without waiting for laboratory results since some patients are “lost” over this period as they do not return to health facilities for their test results and treatment.

A challenge with treating STIs according to symptoms rather than laboratory results is that many STIs present with similar symptoms. This can lead to misdiagnosis and incorrect treatment as well as asymptomatic infections going undiagnosed and untreated.

Thus, without lab testing, combined with routine STI screening to identify asymptomatic cases, it is difficult to understand the true burden of gonorrhoea in the country or to measure the extent of drug resistance.

A systematic review, however, indicates that while azithromycin resistance is a challenge in South Africa, there was not yet evidence of ceftriaxone resistance as of 2022.

The National Institutes of Communicable Diseases (NICD) classified ceftriaxone-resistant gonorrhoea a notifiable condition in 2017, meaning that any diagnosed cases must be reported to it. The NICD did not respond to a query from Spotlight as to whether there have been any confirmed cases of ceftriaxone-resistant gonorrhoea in South Africa to date.

While South Africa is not yet facing a ceftriaxone-resistance crisis, experts are of the view that it is only a matter of time before this public health challenge reaches our borders, as global cases are increasing and the drug-resistant strain is transmittable.

Some access to zoliflodacin

Given the risk of a ceftriaxone-resistance crisis, it is important that the two new antibiotics, zoliflodacin and gepotidacin, become available here as soon as possible. These new antibiotics have quite different histories.

Zoliflodacin was developed by GARDP – a non-profit organisation working to accelerate the development of new antibiotics – together with the private biopharmaceutical company Innoviva.

In November 2023, GARDP shared the results of its phase 3 trial of zoliflodacin, which took place in South Africa, Thailand, Belgium, the Netherlands and the United States. It tested the effectiveness of a single dose of oral zoliflodacin compared with the current standard of care treatment for gonorrhoea, which is an injection of ceftriaxone combined with oral azithromycin.

The trial showed that a single dose of zoliflodacin works just as well as the standard of care. The results have not yet been published in a peer-reviewed journal.

Zoliflodacin has also “been shown to be active against all multidrug-resistant strains of Neisseria gonorrhoeae (the gonorrhoea bacteria), including those resistant to ceftriaxone, the last remaining recommended antibiotic treatment”, GARDP’s R&D Project Leader for STIs, Pierre Daram, told Spotlight.

He added that Innoviva is in the process of applying to get the greenlight to use zoliflodacin in the United States. At the same time, GARDP is planning to apply for approval in some of its own regions, starting with Thailand and South Africa.

GARDP is also working on a programme to make the unregistered drug available for patients who have no other treatment options.

“The zoliflodacin managed access programme is about to be activated,” Daram said. “The aim is to provide early access to zoliflodacin, prior to regulatory approval in a country, in response to individual patient requests by clinicians and whereby certain regulatory and clinical criteria are met.” South Africa will be one of the countries covered under this programme, said Daram.

He explained that individual patient requests for treatment will be received from treating clinicians through an online platform. “Based on information provided by the clinician and certain pre-determined regulatory and clinical criteria being met, GARDP will make a case-by-case decision as to whether zoliflodacin will be made available.” Daram added: “Consideration is given to both clinical as well as diagnostic criteria for documentation of treatment failure.”

Access to gepotidacin remains uncertain

Shortly after results for zoliflodacin were announced, GlaxoSmithKline (GSK) also shared positive findings for their new antibiotic in treating gonorrhoea. In April 2024, the company reported that a phase 3 trial showed that taking two doses of oral gepotidacin worked just as well as the standard treatment.

The results of this trial, which was conducted in Australia, Germany, Mexico, Spain, the United Kingdom, and the United States, were published in the Lancet medical journal in May.

While gepotidacin represents an important new treatment option for gonorrhoea, there is no indication that it will be available in South Africa any time soon.

Gepotidacin has not yet been registered for the treatment of gonorrhoea but was approved in March in the United States for treating uncomplicated urinary tract infections (UTIs) in women and girls over 12. The medicine will thus have a much larger market in the US than if it was only registered for treating gonorrhoea.

The price that GSK will charge for gepotidacin has not yet been disclosed, but a spokesperson told Spotlight it is set to be launched in the US in the second half of 2025.

“[T]he price in the US will be disclosed when the product will be commercialized,” said the GSK spokesperson.

The company did not respond to Spotlight’s questions regarding the company’s plans to register and market gepotidacin in South Africa.

What happens next?

With the launch of the zoliflodacin managed access programme, clinicians in South Africa will soon be able to apply for the medicine for patients that are resistant to existing drugs. Given that ceftriaxone-resistance is rare in the country, the number of patients in the country that will be eligible for zoliflodacin is likely to be small.

Securing broader access to zoliflodacin or gepotidacin, potentially for use as a first line gonorrhoea treatment appears to be a long way off. While GARDP is planning to file for registration of zoliflodacin in South Africa, GSK has not indicated whether they will follow suit for gepotidacin.

Providing the new antibiotics for first line gonorrhoea treatment could expand delivery and uptake, as the new drugs are both oral tablets and would remove the need for an injection to treat gonorrhoea, said Professor Nigel Garrett, who is the Chief Scientific Officer at the Desmond Tutu Health Foundation.

If zoliflodacin and gepotidacin are approved and made affordable in South Africa, they could also play a vital role in strengthening the country’s efforts to preserve the long-term effectiveness of other antibiotics.

Ceftriaxone “is a really important drug to keep, [to] make sure that there isn’t too much resistance against it,” Garret told Spotlight. He explained that the medicine is needed to treat sepsis occurring in hospitals, as well as meningitis.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Categories : Cardiovascular DiseaseTags :

Combination Therapy can Prolong Life in Severe Heart Disease

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Human heart. Credit: Scientific Animations CC4.0

Aortic valve narrowing (aortic stenosis) with concomitant cardiac amyloidosis is a severe heart disease of old age that is associated with a high risk of death. Until now, treatment has consisted of valve replacement, while the deposits in the heart muscle, known as amyloidosis, often remain untreated. An international research consortium led by MedUni Vienna and University College London has shown for the first time that combined treatment consisting of heart valve replacement and specific drug therapy offers a significant survival advantage for patients. The study results have been published in the European Heart Journal.

As part of the study conducted by the research team led by Christian Nitsche (MedUni Vienna) and Thomas Treibel (University College London), data from 226 patients with aortic stenosis and concomitant cardiac amyloidosis from ten countries were examined. Aortic stenosis is a narrowing of the heart valve that directs blood from the left ventricle into the bloodstream. In cardiac amyloidosis, misfolded proteins are deposited in the heart muscle. Both diseases occur in older people and often together. Until now, it was unclear whether treating amyloidosis in addition to valve surgery would benefit patients.

The analysis now published showed that both aortic valve replacement and treatment with the drug tafamidis for amyloidosis were associated with a significantly lower risk of death. The survival benefit was highest in patients who received both forms of treatment. “Our results even show that patients with both conditions who received valve replacement and specific amyloidosis therapy had similar long-term survival rates to people with aortic stenosis without amyloidosis,” emphasises study leader Christian Nitsche.

Targeted tests necessary

Both aortic stenosis and cardiac amyloidosis impair the heart’s pumping function and can lead to death if left untreated. Targeted therapy can slow the progression of amyloidosis, while valve replacement treats the mechanical stress caused by the narrowed heart valve. Around ten percent of patients with aortic stenosis also have amyloidosis, but this is often not diagnosed in everyday clinical practice. “Our findings also suggest that patients with severe aortic valve stenosis should be screened for amyloidosis so that we can offer them targeted life-prolonging treatment options,” emphasises Christian Nitsche.

Source: Medical University of Vienna

Categories : Cancer GastrointestinalTags :

New Findings Reveal Immune Molecules that Drive Inflammatory Bowel Disease

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Chronic inflammatory bowel disease is challenging to treat and carries a risk of complications, including the development of bowel cancer. Young people are particularly affected: when genetic predisposition and certain factors coincide, diseases such as ulcerative colitis or Crohn’s disease usually manifest between the ages of 15 and 29 – a critical period for education and early career development. Prompt diagnosis and treatment are crucial. Researchers at Charité – Universitätsmedizin Berlin have now discovered a therapeutic target that significantly contributes to halting the ongoing inflammatory processes. Their findings are published in the current issue of the journal Nature Immunology*.

Sometimes gradually, sometimes in flare-ups – accompanied by severe abdominal cramps, diarrhoea, weight loss, fatigue and a high level of emotional stress – this is how the two most common chronic inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, often begin. While ulcerative colitis only affects the inner lining of the large intestine, Crohn’s disease can involve the entire thickness of the intestinal wall, most commonly in the small intestine, but sometimes also the stomach and oesophagus. Ongoing inflammation can cause lasting tissue damage and increase the risk of cancer. While traditional treatments aim to suppress the immune system as a whole, newer therapies are more targeted: they interrupt the inflammatory process by blocking specific messenger substances that drive inflammation in the body.

The exact causes of severe systemic diseases are still not fully understood. In addition to genetic factors, environmental influences are also believed to play an important role in their development. Prof Ahmed Hegazy has been studying inflammatory processes in the gut and the immune system’s defence mechanisms at Charité’s Department of Gastroenterology, Infectiology and Rheumatology for several years. Together with his team, he has now succeeded in identifying the interaction between two messenger substances of the immune system as the driving force behind chronic intestinal inflammation: Interleukin-22, a protein that supports the cells lining the inside of the gut and helps maintain the protective barrier, and oncostatin M, a signalling molecule that plays a significant role in tissue repair and cell differentiation.

Uncontrolled chain reaction

“At the clinic, we mainly see young patients who just beginning their professional lives. So far, we have only been able to slow down the progression of the disease and alleviate symptoms. But not all patients respond well to existing treatments, so new therapeutic approaches are urgently needed,” says Ahmed Hegazy. In previous work, the research team closely examined the effects of oncostatin M, an inflammation-promoting messenger molecule. This protein, produced by certain immune cells, activates other inflammatory factors – setting off a chain reaction that triggers an excessive immune response. “It was especially interesting for us to see that patients with high levels of oncostatin M do not respond to several common therapies,” Ahmed Hegazy explains. “This means that Oncostatin M levels could help predict treatment failure and may serve as a biomarker for more severe disease. That’s exactly where we focused our efforts: we wanted to understand this signaling pathway better and find ways to block it with targeted treatments.”

The research team spent five years uncovering how the immune messenger oncostatin M triggers inflammatory responses. They began by using animal models, and later studies tissue samples from patients, to examine the different stages of chronic intestinal diseases, State-of-the-art single-cell sequencing showed that – compared to healthy tissue – a much larger number of unexpected cell types in the inflamed gut have receptors for oncostatin M. At the same time, additional immune cells start producing the inflammatory protein. Interestingly, interleukin-22, which normally protects tissue, also makes the gut lining more sensitive to oncostatin M by increasing the number of its receptors. “These two immune messengers work together and amplify the inflammation, drawing more immune cells into the intestine, like a fire that keeps getting more fuel and spreads,” as Ahmed Hegazy relates. “In our models, we specifically blocked the binding sites for oncostatin M and saw a clear reduction in both chronic inflammation and the associated of cancer.”

Targeted therapy for high-risk patients in sight

The researchers found a particularly high number of receptors for the messenger molecule oncostatin M around the tumours in tissue samples from patients with colorectal cancer caused by chronic intestinal inflammation, but not in the surrounding healthy tissue. This observation suggests that this signalling pathway may help promote cancer development. But chronic inflammation does not always lead to bowel cancer, and not every patient is affected in the same way, making treatment and prognosis difficult. With an understanding of oncostatin M’s amplifying effect on interleukin-22, new therapies may be possible.

The team’s experimental findings may soon translate into a real-world therapy: by specifically disrupting the harmful interaction between the immune messengers interleukin-22 and oncostatin M. “Our results provide a strong scientific basis for developing targeted treatments against this inflammation-promoting mechanism in chronic inflammatory bowel disease — particularly in patients with more severe forms of the illness,” explains Ahmed Hegazy. A clinical trial is already underway to test an antibody that blocks the receptors for Oncostatin M.

Source: Charité – Universitätsmedizin Berlin

Categories : Cancer General InterestTags :

Immune System the Focus of PhD’s Research at UKZN

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Elated at graduating with a doctoral degree is Dr Aviwe Ntsethe. Credit: University of KwaZulu-Natal

Dr Aviwe Ntsethe’s curiosity in the Medical field deepened when he started exploring the complexities of human physiology and the crucial role of the immune system in cancer, leading to him graduating with a PhD.

Growing up in the small town of Bizana in the Eastern Cape, Ntsethe attended Ntabezulu High School, where his passion for Medical Science took root. Despite facing significant challenges, including limited funding opportunities for his studies, he remained determined to advance in the discipline.

Throughout his PhD journey at UKZN, Ntsethe had to juggle multiple jobs to support himself and his studies while conducting his research. He worked at Netcare Education and the KwaZulu-Natal College of Emergency Care, and later took up a position as a contractual laboratory technician in the Department of Physiology at UKZN. It was with the guidance of his PhD supervisor, Professor Bongani Nkambule, that he learned critical work ethics and advanced laboratory techniques. The co-supervision of Professor Phiwayinkosi Dludla further enriched his research experience and contributed to his academic growth.

Ntsethe’s thesis focused on investigating B cell function and immune checkpoint expression in patients with Chronic Lymphocytic Leukaemia (CLL). The study found that patients with CLL had higher levels of immune checkpoint proteins in their B cell subsets, which play a crucial role in regulating the immune system.

Furthermore, using monoclonal antibodies that target these immune checkpoints, he found these patients could potentially benefit from immunotherapy. Specifically, immunotherapy may improve the function of B cells, key players in fighting infections and cancers, thereby offering new hope for better outcomes in patients with CLL.

He has published three papers from this study. ‘I am excited and proud when I reflect on my achievement of completing this significant journey which was both challenging and rewarding, pushing me to expand my knowledge and skills in ways I never imagined.’

Now, a lecturer at Nelson Mandela University, Ntsethe is committed to mentoring the next generation of Medical scientists. He continues to use the invaluable knowledge and experience he gained during his PhD studies to inspire students and cultivate their passions in research and health sciences. Looking ahead, Ntsethe hopes to expand his research, focusing on immune system interactions in chronic diseases while also encouraging students from diverse backgrounds to pursue careers in Medical Science.

Outside academia, Ntsethe enjoys travelling, staying physically active through workouts, playing chess and indulging in coding or programming.

Source: University of KwaZulu-Natal

Categories : Neurology UrogenitalTags :

Brain Stimulation and Mindfulness Exercises Could Reduce ‘Latchkey Incontinence’

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Urinary incontinence. Credit: Scientific Animations CC4.0

Arriving home after a long day may be a relief, but for some people, seeing their front door or inserting a key into the lock triggers a powerful urge to pee. Known as “latchkey incontinence,” this phenomenon is the subject of a new study by researchers at the University of Pittsburgh who found that mindfulness training and/or non-invasive brain stimulation could reduce bladder leaks and feelings of urgency evoked by these cues. 

The findings of the pilot study, the first evaluation of brain-based therapies for urinary incontinence, are published in the latest issue of the journal Continence. 

“Incontinence is a massive deal,” said senior author Dr. Becky Clarkson, research assistant professor in the Pitt School of Medicine Division of Geriatrics and co-director of the Continence Research Center. “Bladder leaks can be really traumatizing. People often feel like they can’t go out and socialise or exercise because they’re worried about having an accident. Especially for older adults, this feeds into social isolation, depression and functional decline. Our research aims to empower people with tools to get back their quality of life.” 

Latchkey incontinence, or situational urgency urinary incontinence, is bladder leakage triggered by specific environments or scenarios. Common cues include one’s front or garage door, running water, getting into a car or walking past public restrooms. 

According to lead author Dr. Cynthia Conklin, associate professor in the Pitt Department of Psychiatry, latchkey incontinence is a type of Pavlovian conditioning. Like Pavlov’s dogs, which salivated upon hearing a bell that they associated with food, years of going to the bathroom immediately upon entering the house can condition one to feel strong bladder urgency when seeing the front door.

In a previous study, Clarkson and Conklin showed participants pictures of their own front doors or other triggers versus “safe” images of things that did not evoke urgency while they had an MRI of their brain. A part of the brain called the dorsolateral prefrontal cortex was more active when participants viewed urgency-related images.  

“The prefrontal cortex is the seat of cognitive control,” said Clarkson. “It’s the executive function center of the bladder, the bit that is telling you, ‘Okay, it’s time to go. You should find somewhere to go.’” 

The researchers hypothesised that activating this part of the brain during exposure to urgency cues, through mindfulness and/or with transcranial direct current stimulation (tDCS) of the brain, could improve participants’ ability to regulate responses to these cues and control urgency and leakage.  

They recruited 61 women aged over 40 who reported regular situationally triggered bladder leaks and randomly assigned them to one of three groups: Participants either listened to a 20-minute mindfulness exercise, received tDCS or both while viewing personal trigger photos.  

The mindfulness exercise, developed by coauthor Dr Carol Greco, associate professor of psychiatry and physical therapy at Pitt, was like a typical body scan practice that instructs participants to move through their body, bringing attention to each part in turn. But unlike most body scans, it included specific acknowledgment of bladder sensation.  

After completing four in-office sessions over five to six days, participants in all three groups experienced reduced urgency when they viewed trigger cues. Women in all three groups also reported an improvement in the number of urgency episodes and leaks after completing the sessions. 

Although this pilot study did not have a control group, for comparison, the researchers say that the magnitude of improvement from tDCS and mindfulness was similar to what other research has reported for interventions such as medications and pelvic floor therapy.  

“Although we need to do more research, these results are really encouraging because they suggest that a behavioral tool like mindfulness can be an alternative or additional way to improve symptoms,” said Conklin. “Balancing multiple prescriptions is a big issue among older adults, and a lot of people are reluctant to take another medication, so I think that’s one of the reasons that we saw such high acceptability of non-pharmacologic interventions in this study.” 

More than 90% of recruited participants completed the study.  

“Participants loved it,” said Clarkson. “Almost everyone who started the study finished it, even though coming into the office four days within one week was quite a big commitment. We got really great feedback, and a lot of women told us that they continue to use the mindfulness exercise in their daily lives.” 

“For the first time in 20 years of doing research, we got thank you cards!” added Conklin. “I think that incontinence is such a taboo subject, and a lot of people find it difficult to talk about, so they often don’t even realize that there are treatments out there. But you don’t have to suffer in silence.” 

Now, the researchers are planning to explore whether the mindfulness component of the study could be helpful in independent living facilities to reach a wide range of older adults. They also hope to eventually develop an app-based tool for smartphones. 

Source: University of Pittsburgh

Categories : Genetics Neurodegenerative DiseasesTags :

Common Gene Variant Doubles Dementia Risk for Men

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New research has found that men who carry a common genetic variant are twice as likely to develop dementia in their lifetime compared to women. The research, published in Neurology, used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial to investigate whether people who had variants in the haemochromatosis (HFE) gene, which is critical for regulating iron levels in the body, might be at increased risk of dementia.

Co-author Professor John Olynyk, from the Curtin Medical School, said one in three people carry one copy of the variant, known as H63D, while one in 36 carry two copies.

“Having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not women,” Professor Olynyk said.

“While the genetic variant itself cannot be changed, the brain pathways which it affects – leading to the damage that causes dementia – could potentially be treated if we understood more about it.”

Professor Olynyk said further research was needed to investigate why this genetic variant increased the risk of dementia for males but not females.

“The HFE gene is routinely tested for in most Western countries including Australia when assessing people for haemochromatosis – a disorder that causes the body to absorb too much iron. Our findings suggest that perhaps this testing could be offered to men more broadly,” Professor Olynyk said.

“While the HFE gene is critical for controlling iron levels in the body, we found no direct link between iron levels in the blood and increased dementia risk in affected men.

“This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body.”

The ASPREE trial was a double-blind, randomised, placebo-controlled trial of daily low-aspirin in 19 114 healthy older people in Australia and the USA. Primarily undertaken to evaluate the risks versus benefits of daily low-dose aspirin in this cohort, it created a treasure trove of healthy ageing data that has underpinned a wealth of research studies.

Source: Curtin University

Categories : AgeingTags :

Could ‘Pausing’ Necrosis be the Final Frontier in Ageing and Medicine?

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Necrosis, unprogrammed cell death, spews a host of toxic molecules into the cellular environment. Credit: University College London

In a new study, published in Oncogene, a world-leading international team of scientists and clinicians explore the potential of necrosis to reshape our understanding and treatment of age-related conditions and even protect astronauts on longer journeys into space.

Challenging prevailing views, the paper brings together evidence from cancer biology, regenerative medicine, kidney disease, and space health to argue that necrosis is not merely an endpoint, but a key driver of aging that presents an opportunity for intervention.

Dr Keith Siew, an author of the study from UCL Centre for Kidney & Bladder Health, said: “Nobody really likes talking about death, even cell death, which is perhaps why the physiology of death is so poorly understood. And in a way necrosis is death. If enough cells die, then tissues die, then we die. The question is what would happen if we could pause or stop necrosis.”

Dr Carina Kern, lead author of the study and CEO of LinkGevity, a biotech company based at Cambridge’s Babraham Research Campus and part of the NASA Space-Health program, said: “Necrosis remains one of the last frontiers in medicine – a common thread across aging, disease, space biology, and scientific progress itself.”

Cells are the fundamental building blocks of life and can die in various ways. ‘Programmed’ forms of cell death are beneficial, carefully orchestrated processes that allow our tissues to replenish themselves and function well throughout life.

But ‘unprogrammed’ cell death, or necrosis, is an uncontrolled and catastrophic process that leads to tissue degeneration and biological decline.

At the centre of the necrotic process is calcium, a vital resource that effectively controls the cell by determining which functions are switched on or off. Calcium ions are normally maintained at a level that is 10 000 to 100 000 times higher outside the cell than inside.

When this finely tuned balance fails, calcium floods the cell like an electrical short circuit, pushing the cell into chaos. Unlike programmed death, where cells dismantle in an orderly manner, necrosis causes cells to rupture, spilling toxic molecules into surrounding tissues.

This sparks a chain reaction that causes widespread inflammation and affects tissue repair, creating a snowball effect that ultimately leads to frailty and the onset of chronic age-related conditions such as kidney disease, heart disease and Alzheimer’s.

Dr Siew added: “When cells die, it’s not always a peaceful process for the neighbours.”

Dr Kern explains: “Necrosis has been hiding in plain sight. As a final stage of cell death, it’s been largely overlooked. But mounting evidence shows it’s far more than an endpoint. It’s a central mechanism through which systemic degeneration not only arises but also spreads. That makes it a critical point of convergence across many diseases. If we can target necrosis, we could unlock entirely new ways to treat conditions ranging from kidney failure to cardiac disease, neurodegeneration, and even aging itself.”

Notably, it is in the kidneys that necrosis may have its most devastating and underappreciated impact. Necrosis induces kidney disease, which can lead to kidney failure requiring a transplant or dialysis. By age 75 nearly half of all individuals develop some degree of kidney disease as part of the natural aging process.

Dr Siew added: “With kidney disease, there’s no one underlying reason that the kidneys fail. It could be a lack of oxygen, inflammation, oxidative stress, a build-up of toxins, and so on. All of these stressors eventually lead to necrosis, which initiates a positive feedback loop that spirals out of control, leading to kidney failure. We can’t stop all of these stressors, but if you could intervene at the point of necrosis, you’d effectively achieve the same result.”

Another area where interrupting necrosis could have a big impact is spaceflight, where astronauts often experience accelerated ageing and kidney-related decline due to the effects of low gravity and exposure to cosmic radiation. A 2024 study involving Dr Siew demonstrated that the human kidney may be the ultimate bottleneck for long-duration space missions.

The authors say finding solutions to this accelerated aging and kidney disease may be the final frontier for human deep space exploration.

Dr Kern said: “In many age-related diseases – affecting diverse organs such as the lungs, kidneys, liver, brain, and cardiovascular system – relentless cascades of necrosis fuel the progression of disease. This is often alongside impaired healing that leads to fibrosis, inflammation and damaged cells. Each cascade triggers and amplifies the next.

“If we could prevent necrosis, even temporarily, we would be shutting down these destructive cycles at their source, enabling normal physiological processes and cell division to resume – and potentially even allowing for regeneration.”

Source: University College London