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Novel nanomedicine developed for rheumatoid arthritis

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Patients with rheumatoid arthritis have unique autoantibody patterns

A team of researchers from the LKS Faculty of Medicine, the University of Hong Kong (HKUMed) has developed a novel cinnamaldehyde-based prodrug nanomedicine for rheumatoid arthritis by utilising cinnamaldehyde, a common food additive, as an anti-inflammatory agent.

The novel prodrug forms nanoparticles that deliver the therapeutic agents precisely to the inflamed sites, offering a solution for the treatment of inflammatory diseases like rheumatoid arthritis.

Inflammation is a biological self-response mechanism to protect the human body from injury and infection caused by harmful stimuli. Generally, an inflammatory response can assist the body in self-defence and repair. However, dysregulated inflammatory responses may result in the development of various inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease.

The primary cause of these conditions involves the loosening of endothelial junctions, which allows inflammatory cell recruitment and infiltration into inflamed tissue.

This lead to activated inflammatory cells promoting the overproduction of various pro-inflammatory cytokines, which are responsible for the initiation and progression of inflammatory lesions. Therefore, the suppression of excessive pro-inflammatory cytokines is essential for the prevention, alleviation, and treatment of various inflammatory diseases.

As the disease progresses, the deterioration of the joints significantly impairs their ability to function, causing irreversible damage to their health and quality of life.

The current treatment strategies for inflammatory diseases involve primarily the use of anti-inflammatory medications, including non-steroidal anti-inflammatory drugs, steroids, and biological agents.

In severe cases, surgical intervention may be required as an adjunct therapy. Despite remarkable advances in anti-inflammation and relief of clinical symptoms, the current treatment approach has been restricted by insufficient therapeutic efficacy and unfavourable systemic adverse effects due to the lack of targeting ability, poor stability, and low water solubility.

Research findings and significance

Through chemical modification, the research team transformed cinnamaldehyde into a reactive oxygen species-responsive polymeric prodrug that can self-assemble into nanoparticles. In experiments on two mouse models with RA and ulcerative colitis, the researchers found that these nanoparticles effectively accumulated at inflamed sites of the mice through intravenous injection.

The accumulated nanoparticles released cinnamaldehyde in response to high concentrations of reactive oxygen species at the inflamed sites, which alleviated the progression of inflammation by inhibiting the overproduction of pro-inflammatory cytokines.

The results from the mouse model studies demonstrated that the cinnamaldehyde prodrug nanomedicine can be precisely delivered to the inflamed sites, unleashing their therapeutic effects without causing damage to other normal tissues.

Professor Wang Weiping, Associate Professor of Dr Li Dak-Sum Research Centre and Department of Pharmacology and Pharmacy, HKUMed, and the research member of the State Key Laboratory of Pharmaceutical Biotechnology, HKU, who led the research project, pointed out that this technology has three major benefits.

“First, the team transformed cinnamaldehyde into a prodrug form through chemical modification, which can effectively improve the solubility and stability of the drug, making it easier for the body to absorb and maintain its activity,” Professor Wang Weiping explained.

“Second, administering the drug in a nanoparticle form increases the accumulation of the drug at the site of inflammation, avoiding rapid metabolism of the drug and enhancing its therapeutic efficacy. Third, reactive oxygen species at the inflamed site can activate the drug to exert its effects in the affected area. The cinnamaldehyde prodrug has a better therapeutic efficacy than traditional drugs, providing a groundbreaking approach for targeted drug delivery in the treatment of inflammatory diseases.”

Professor Wang and his team are currently working on developing an oral dosage form of cinnamaldehyde prodrugs, to help patients easily comply with their doctor’s instructions for medication and promote future clinical translation.

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Two teas or coffees a day could lower dementia risk, experts say

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People who drink two to three cups of coffee or tea daily have a lower dementia risk, new research suggests.

Health records for more than 130,000 people showed that over 40 years, those who routinely drank two to three cups of caffeinated coffee or one to two cups of caffeinated tea daily had a 15 to 20 per cent lower risk compared with those who went without.

The caffeinated coffee drinkers also reported slightly less cognitive decline, a measure of how thinking and memory deteriorate over time, than those who opted for decaf and performed better on some objective tests of brain function.

The findings suggest habitual tea and coffee drinking may be good for the brain, but the research cannot prove it, as caffeine drinkers may be less prone to dementia for other reasons.

The study was led by Yu Zhang, who studies nutritional epidemiology at Harvard University.

A similar link would arise if poor sleepers, who appear to have a greater risk of cognitive decline, steered clear of caffeine to get a better night’s rest.

“Our study alone can’t prove causality, but to our knowledge, it is the best evidence to date looking at coffee and tea intake and cognitive health, and it is consistent with plausible biology,” Zhang said.

Coffee and tea contain caffeine and polyphenols, plant compounds that may protect against brain ageing by improving vascular health and reducing inflammation and oxidative stress, where harmful atoms and molecules called free radicals damage cells and tissues.

Substances in the drinks could also work by improving metabolic health. Caffeine, for example, is linked to lower rates of type 2 diabetes, a known risk factor for dementia.

The researchers analysed records of 131,821 volunteers enrolled in two big US public health studies, the Nurses’ Health Study and the Health Professionals Follow-up Study.

Both took repeated assessments of the participants’ diets, dementia diagnoses, any cognitive decline they experienced and scores on objective cognitive tests for up to 43 years.

Overall, men and women who drank the most caffeinated coffee had an 18 per cent lower risk compared with those who had little or none, with similar results seen for tea.

The effect seemed to plateau at two to three cups of caffeinated coffee or one to two cups of caffeinated tea. No link was found between decaffeinated coffee and dementia.

Further work is needed to confirm whether the two drinks actually protect the brain.

Gold standard trials that randomly assign people to drink caffeinated or decaffeinated drinks for decades before checking for differences in dementia diagnoses are largely impractical.

However, studies could explore whether the drinks drive biological changes linked to brain function, which could be spotted in scans or other tests, Zhang said.

Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow, said getting clarity would not be easy, not least because caffeine can have good and bad effects on the brain.

Tea and coffee both contain antioxidants that may be beneficial, and a caffeine boost can motivate people to work, learn and exercise.

In some people, caffeine raises blood pressure, a significant driver of dementia.

“Caffeine does a multitude of things, some which may be beneficial, some which may be harmful, and the net effect can never be estimated until you do a randomised trial,” Sattar said.

Researchers believe about half of dementia cases worldwide can be prevented or delayed by tackling factors such as obesity, smoking, excessive alcohol consumption, hearing loss and high blood pressure.

“Don’t think of coffee or tea as a magic shield,” Zhang said.

“I’d say maintaining a healthy lifestyle, getting regular exercise, having a balanced diet and getting good sleep are all important to get better brain health.”

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Genetic influence on lifespan underestimated by half

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People are twice as likely to inherit their lifespan as previously thought, new research suggests.

The genetic contribution to how long a person lives is around 50 per cent, based on health databases in Denmark and Sweden. This reflects heritability, the share of lifespan differences due to genes.

For decades, many scientists believed genes and ancestry accounted for between about 10 and 25 per cent of longevity.

The research was led by scientists at the Weizmann Institute in Israel, with the Karolinska Institute in Sweden and Leiden University.

The earlier underestimates arose from limited historic health and mortality data, where deaths due to war, infectious disease, risky or unsafe work, accidents, poor diet and lack of medical care were hard to separate in records.

“For many years, human lifespan was thought to be shaped almost entirely by non-genetic factors, which led to considerable scepticism about the role of genetics in ageing and about the feasibility of identifying genetic determinants of longevity,” said Ben Shenhar of the Weizmann Institute.

Environmental forces such as disease or living conditions can mask or confound potential genetic effects.

Hereditary causes of death, for those not killed first by external causes, mean “processes originating within the body, including genetic mutations, age-related diseases and the decline of physiological function with age.” the researchers said.

“If heritability is high, as we have shown, this creates an incentive to search for gene variants that extend lifespan, in order to understand the biology of ageing and, potentially, to address it therapeutically.” said Shenhar.

Other recent research has pointed to a potential role for taurine, an amino acid, in slowing the ageing process.

Scientists have also highlighted the bowhead whale’s 200-year lifespan, attributed to a cellular protein that may protect against carcinogenic mutations.

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Aerska raises US$39m for brain RNA medicines

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Biotechnology company Aerska has raised US$39m in Series A funding to develop brain-delivered RNA medicines.

The company is developing treatments for neurological diseases, including genetically driven forms of Alzheimer’s disease.

This takes Aerska’s total funding to US$60m, months after its seed funding announcement in October 2025.

The company’s platform uses what it calls “brain shuttle” technology to help RNA therapeutics cross the blood-brain barrier, a protective membrane that normally prevents many drugs reaching the brain. RNA interference is a biological process where RNA molecules can silence or reduce the activity of specific genes.

The approach is designed to allow intravenous or subcutaneous administration, with the aim of achieving uniform brain distribution.

The financing was led by EQT Dementia Fund and age1, with participation from Iaso Ventures, alongside existing investors.

Chief executive and co-founder Jack O’Meara said: “The ability to systemically administer RNAi therapies to the brain unlocks a powerful new approach to treating neurodegeneration.

“Partnering with EQT Dementia Fund further strengthens our path to the clinic as we work to translate this capability into meaningful therapies for the treatment of genetically-driven forms of Alzheimer’s disease and other devastating brain disorders.”

As part of the financing, Arno de Wilde, managing director at EQT, Philip Scheltens, partner and head of the Dementia Fund at EQT, and Alex Colville, general partner at age1, will join Aerska’s board of directors.

Scheltens said: “For families facing diseases like Alzheimer’s, Aerska’s approach offers hope for preserving cognitive function and quality of life.

“The team’s strategy of upstream intervention, combined with a focus on the genetic forms of neurological disease, positions them to transform outcomes for populations who have been underserved by current therapeutic approaches.

“We really look forward to working with this talented team to advance this groundbreaking platform.”

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