Tag: 22/10/25

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New Antivirals Could Help Prevent HSV-1 by Changing Cell Structures

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Lab tests confirm that antiviral class known as Pin1 inhibitors could reduce and stop outbreaks of herpes simplex virus-1

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A class of antivirals called Pin1 inhibitors could reduce or stop outbreaks of herpes simplex virus 1 (HSV-1), the common infection behind oral herpes, according to new research published in Antiviral Research.

HSV-1 causes sores around the mouth, commonly called cold sores or fever blisters. Most people are infected with HSV-1 in childhood, and between 50% and 90% of people worldwide have HSV-1. After the initial infection, HSV-1 remains in the body and can reactivate throughout a person’s life. While HSV-1 infections are usually mild, they can be serious and even deadly for people with suppressed immune systems. Finding new, more effective antivirals for this common illness is essential. 

Pin1 inhibitors suppress HSV-1 replication by inhibiting viral protein synthesis and preventing nucleocapsid egress from the nucleus. (Takemasa Sakaguchi/Hiroshima University)

Researchers focused on an enzyme called peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, or Pin1, that regulates protein stability, function, and cellular structure. When this enzyme is dysregulated, it can play a role in a variety of conditions, including obesity, cancer, heart failure, and more. Viruses, such as cytomegalovirus (CMV) and SARS-CoV-2, are known to affect Pin1, and Pin1 inhibitors have been developed to reduce the impact of these viruses. 

Because HSV-infected cells over-express Pin1, researchers wanted to know if Pin1 inhibitors could also be used to treat HSV-1. “This study revealed that the host factor Pin1 is a crucial therapeutic target for the proliferation of HSV-1. Pin1 inhibitors potently suppress HSV-1 replication at low concentrations,” said Takemasa Sakaguchi, a professor at the Graduate School of Biomedical and Health Sciences at Hiroshima University in Hiroshima, Japan. 

In laboratory tests, the Pin1 inhibitor H-77 and the four newly developed Pin1 inhibitors successfully stopped the replication of HSV-1. VeroE6 cells, derived from the kidney of an African green monkey and commonly used in virology research, were infected with HSV-1 and cultured in the presence of different amounts of a Pin1 inhibitor. As the amount of the inhibitor increased, the effects of HSV-1 on the cells became less pronounced and completely disappeared at 1 μM. They also found that any viral particles released from the treated cells were non-infectious. 

The most important finding is how Pin1 inhibitors affect cell structures to prevent the virus from escaping. They do this by stabilising nuclear membrane structure, physically trapping the virus in the cell nucleus. “The nuclear lamina initially functions as a ‘barrier’ when nucleocapsids of progeny viruses, that replicate within the nucleus, bud from the nuclear membrane. Pin1 overexpressed by the virus removes this barrier. However, through the action of the Pin1 inhibitor H-77, this barrier is rather reinforced, forming a thick and robust lamina layer. This demonstrates that H-77 transforms the nuclear lamina into an ‘impregnable defensive wall,’ physically blocking the escape of viruses from the nucleus of the cell,” said Sakaguchi.

Looking ahead, researchers will continue to evaluate the effectiveness of Pin1 inhibitors to treat HSV-1. They will also research how Pin1 inhibitors could be used to treat other viruses. “The ultimate goal for the future is to aim for the clinical application of Pin1 inhibitors as ‘host-directed therapeutics,’ which are less likely to cause drug resistance. To achieve this, we will first evaluate their efficacy against diverse viruses to clarify the treatable range. Simultaneously, research to optimise the compound structure is essential for creating more potent and selective drugs,” said Sakaguchi. 

Source: University of Hiroshima

Categories : Ageing NeurologyTags : Leave a comment

Quitting Smoking Late in Life May Still Slow Cognitive Decline

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Quitting smoking in middle age or later is linked to slower age-related cognitive decline over the long term, according to a new study by UCL researchers.

The study, published in The Lancet Healthy Longevity, looked at data from 9436 people aged 40 or over (average age: 58) in 12 countries, comparing cognitive test results among people who quit smoking with those of a matched control group who kept smoking.

The research team found that the cognitive scores of those who had quit smoking declined significantly less than their smoking counterparts in the six years after they quit. For verbal fluency, the rate of decline roughly halved, while for memory it slowed by 20%.

Since slower cognitive decline is related to reduced dementia risk, their findings add to a growing body of evidence suggesting quitting smoking might be a preventative strategy for the disease. Still, more research is needed to confirm this.

Lead author Dr Mikaela Bloomberg (UCL Institute of Epidemiology & Health Care) said: “Our study suggests that quitting smoking may help people to maintain better cognitive health over the long term even when we are in our 50s or older when we quit.

“We already know that quitting smoking, even later in life, is often followed by improvements in physical health and well-being. It seems that, for our cognitive health too, it is never too late to quit.

“This finding is especially important because middle-aged and older smokers are less likely to try to quit than younger groups, yet they disproportionately experience the harms of smoking. Evidence that quitting may support cognitive health could offer new compelling motivation for this group to try and quit smoking.

“Also, as policymakers wrestle with the challenges of an ageing population, these findings provide another reason to invest in tobacco control.”

Smoking is thought to harm brain health in part because it affects cardiovascular health – smoking causes damage to blood vessels that supply oxygen to the brain. Smoking is also thought to affect cognitive health by causing chronic inflammation and directly damaging brain cells through oxidative stress (due to the creation of unstable molecules called free radicals).

Co-author Professor Andrew Steptoe (UCL Institute of Epidemiology & Health Care) said: “Slower cognitive decline is linked to lower dementia risk. These findings add to evidence suggesting that quitting smoking might be a preventative strategy for the disease. However, further research will be needed that specifically examines dementia to confirm this.”

Previous studies, the researchers noted, had found a short-term improvement in cognitive function after people stopped smoking. But whether this improvement was sustained over the longer term – particularly when people quit smoking later in life – was not known.

To answer this question the research team looked at data from three ongoing studies* where a nationally representative group of participants answered survey questions every two years. The studies covered England, the US, and 10 other European countries.

More than 4,700 participants who quit smoking were compared with an equal number of people who carried on smoking. The two groups were matched in terms of their initial cognitive scores and other factors such as age, sex, education level, and country of birth.

The research team found that the two groups’ scores in memory and verbal fluency tests declined at a similar rate in the six years prior to participants of one group quitting smoking. These trajectories then diverged in the six years following smoking cessation.

For the smokers who quit, the rate of decline was about 20% slower for memory and 50% slower for verbal fluency. In practical terms, this meant that with each year of ageing, people who quit experienced three to four months less memory decline and six months less fluency decline than those who continued smoking.

This was an observational analysis, so unmeasured differences between smokers who quit and continuing smokers could remain; while the trends before quitting were similar, the study cannot prove cause and effect.

However, the research team noted their findings were consistent with earlier studies showing that adults aged over 65 who quit smoking during early- or mid-life have comparable cognitive scores to never smokers, and that former and never smokers have a similar risk of dementia a decade or longer after quitting.

*The longitudinal studies were the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), and the Health and Retirement Study (HRS).

Source: University College London

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mRNA-based COVID Vaccines Improved Responses to Immunotherapy

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Patients with cancer who received mRNA-based COVID vaccines within 100 days of starting immune checkpoint therapy were twice as likely to be alive three years after beginning treatment, according to a new study led by researchers at The University of Texas MD Anderson Cancer Center.

These findings, which include more than 1000 patients treated between August 2019 and August 2023, were presented today at the 2025 European Society for Medical Oncology (ESMO) Congress (Abstract LBA54). The study was led by Steven Lin, MD, PhD, professor of Radiation Oncology, and Adam Grippin, MD, PhD, senior resident in Radiation Oncology.

“This study demonstrates that commercially available mRNA COVID vaccines can train patients’ immune systems to eliminate cancer,” Grippin said. “When combined with immune checkpoint inhibitors, these vaccines produce powerful antitumour immune responses that are associated with massive improvements in survival for patients with cancer.”

How was this association discovered?

The discovery that mRNA vaccines were powerful immune activators came from research conducted by Grippin during his graduate work at the University of Florida in the lab of Elias Sayour, MD, PhD. While developing personalised mRNA-based cancer vaccines for brain tumours, Grippin and Sayour found that mRNA vaccines trained immune systems to eliminate cancer cells, even when the mRNA didn’t target tumours directly.

This finding led to the hypothesis that other types of mRNA vaccines might have the same effect, and the approval and use of mRNA-based COVID vaccines created an opportunity to test this hypothesis. Lin and Grippin initiated a major effort to retrospectively study if MD Anderson patients who received mRNA COVID vaccines lived longer than those who did not receive these vaccines.

How do mRNA COVID vaccines impact immunotherapy responses in cancer?

To better understand the mechanisms at work that can help explain the clinical data, the Lin and Sayour labs at both institutions studied preclinical models. They discovered that mRNA vaccines work like an alarm, putting the body’s immune system on high alert to recognise and attack cancer cells.

In response, the cancer cells start making the immune checkpoint protein PD-L1, which works as a defence mechanism against immune cells. Fortunately, several immune checkpoint inhibitors are designed to block PD-L1, creating a perfect environment for these treatments to unleash the immune system against cancer.

These preclinical observations held up in clinical studies as well. The investigators found similar mechanisms, including immune activation in healthy volunteers and increased PD-L1 expression on tumours in patients who received COVID mRNA vaccines.

While the mechanisms are not yet fully understood, this study suggests COVID mRNA vaccines are powerful tools to reprogram immune responses against cancer.

What are the major implications of this discovery?

“The really exciting part of our work is that it points to the possibility that widely available, low-cost vaccines have the potential to dramatically improve the effectiveness of certain immune therapies,” Grippin said. “We are hopeful that mRNA vaccines could not only improve outcomes for patients being treated with immunotherapies but also bring the benefits of these therapies to patients with treatment-resistant disease.”

A multi-centre, randomised Phase III trial currently is being designed to validate these findings and investigate whether COVID mRNA vaccines should be part of the standard of care for patients receiving immune checkpoint inhibition.

What are the key data from this study on mRNA COVID vaccines and immunotherapy outcomes?

This study included multiple cohorts of several cancer types, evaluating patients who had received an mRNA vaccine within 100 days of starting immunotherapy treatment.

In the first group, 180 patients with advanced non-small cell lung cancer who received a vaccine had a median survival of 37.33 months, compared to 20.6 months in 704 patients who did not receive a vaccine. In a cohort of patients with metastatic melanoma, median survival was 26.67 months in 167 patients who did not receive a vaccine, but it had not yet been reached in 43 patients receiving a vaccine – suggesting a significant improvement.

Importantly, these survival improvements were most pronounced in patients with immunologically “cold” tumors, which would not be expected to respond well to immunotherapy. These patients, who have very low PD-L1 expression on their tumours, experienced a nearly five-fold improvement in three-year overall survival with receipt of a COVID vaccine.

Findings were consistent even when considering independent factors, such as vaccine manufacturer, number of doses, and when patients received treatment at MD Anderson.

Source: University of Texas MD Anderson Cancer Center

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Link Between Calcium Supplements and Dementia Debunked by New Research

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New research has found no evidence that calcium monotherapy increases the long-term risk for dementia.

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New research from Edith Cowan University (ECU), Curtin University and the University of Western Australia has found no evidence that calcium monotherapy increases the long-term risk for dementia, helping to dispel previous concerns about its potential negative effects on brain health in older women.

This study, which leveraged outcomes from prior research that provided calcium supplements or a placebo to 1460 older women over a five-year period, found that the supplement did not increase the long-term risk of dementia.

“Calcium supplements are often recommended to prevent or manage osteoporosis,” said ECU PhD student Ms Negar Ghasemifard.

Around 20 per cent of women over the age of 70 are affected by osteoporosis and calcium supplementation is widely recommended as a preventative measure against fracture.

“Previous research has raised concerns around the impacts that calcium supplements could have on cognitive health, particularly dementia. Results from our study provides reassurance to patients and clinicians regarding the safety of calcium supplements in the context of dementia risk for older women,” Ms Ghasemifard said.

ECU Senior Research Fellow Dr Marc Sim noted that when the analysis was adjusted for supplement compliance, a range of lifestyle factors, including dietary calcium intake and genetic risk, the results remained unchanged.

“Previous research suggesting potential links between calcium supplement use and the risk for dementia was purely observational in nature. Our research, in comparison, consisted of a post-hoc analysis from a 5-year double-blind, placebo controlled randomised clinical trial on calcium supplements to prevent fracture. Whilst our study is still epidemiology, its design does reduce the likelihood of unmeasured confounding”

“Some 730 older women were given calcium supplements over five years, and a further 730 were given placebo. This study design offers more accurate data on dosage and duration, and we had a long follow-up period of 14.5 years, which strengthens our results,” Dr Sim said.

While these findings may alleviate concerns regarding calcium supplementation and all-cause dementia risk in older women, particularly after the age of 80 years, Professor Simon Laws, Director of ECU’s Centre for Precision Health, said further research was required.

“Whether this extrapolates to other demographics, such as men or even women commencing supplementation earlier in life, remains unknown. To confirm the current findings, particularly regarding brain health, and to address these population gaps, future clinical trials of calcium supplements, with or without vitamin D, would need to be undertaken. These should include specific and robust assessments of brain health as the primary outcome measures.”

Curtin University’s Professor Blossom Stephan, Director of the Dementia Centre of Excellence and a Dementia Australia Honorary Medical Advisor said the research highlighted a very important finding that provides reassurance to clinicians and patients about the long-term safety of calcium supplementation.

“Given calcium’s critical role in multiple physiological functions, including bone health, these results provide reassurance that long-term calcium supplementation did not increase dementia risk in older women,” she said.

Source: Edith Cowan University

Categories : Mental HealthTags : Leave a comment

Emotion Plays a Major Role in Psychosis Onset and Persistence

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New research from King’s College London has highlighted the important role that emotions play in the onset and persistence of psychosis.

The research, published in Early Intervention in Psychiatry, advocates for the development of emotion-focused interventions that seek to prevent a person’s relapse in their health as well as maintain their recovery.

Psychosis is a symptom of mental illness typified by hallucinations, delusional thoughts and disorganised thinking. While previous research has implicated emotion in the onset and continuation of psychosis, there has not yet been a universally acknowledged theory to account for the influence that emotions can have on it.

Researchers in this study conducted a systematic review of 78 studies comparing the experiences of healthy controls with individuals at Clinical High Risk (CHR), a diagnosis of schizophrenia (SZ), and those experiencing their First Episode of Psychosis (FEP). Researchers wanted to better understand both the role of emotions, as well as emotional coping strategies, in their experiences.

This systematic review found that SZ and CHR individuals demonstrated significant impairments in their emotional awareness, their understanding of self and others, and their ability to regulate their emotions when compared to healthy controls. They also demonstrated a heightened emotional reactivity.

The researchers, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s, found that individuals with schizophrenia reported high levels of “Negative Affect” – a reduction or absence of normal emotional expression – which was a strong predictor of paranoia.

“Experiencing emotions is a natural part of everyday life. However, our study highlights that people with psychosis experience emotions with more intensity, which can significantly contribute to the emergence and maintenance of their psychosis symptoms. Therefore, psychological interventions that explicitly target emotions and emotional coping in psychosis could help prevent relapse and maintain recovery.”

Dr Anna Georgiades, a Lecturer in Early Intervention in Psychosis at King’s IoPPN and the study’s senior author

The researchers also wanted to explore how individuals at CHR and those with schizophrenia employed coping mechanisms to manage emotional situations. They found that, while the healthy controls were more likely to adopt “Adaptive Coping Strategies”, in which individuals seek to manage stress and difficult situations in healthy and constructive ways, people with psychosis were more likely to employ maladaptive techniques that were associated with an increase in their symptoms and increased depression.

Dr Anna Georgiades, a Lecturer in Early Intervention in Psychosis at King’s IoPPN and the study’s senior author said,  “There are two ways in which a person might manage an emotionally stressful situation; either by removing the stressor, or by seeking to manage the stress that is being caused.

“From the studies we reviewed, we consistently found that people with psychosis used more unhelpful emotional coping such as avoidance and suppression rather than helpful emotional coping such as problem solving or changing the way they think about the situation.

“By reducing unhelpful emotional coping and by increasing more helpful emotional coping (ie, by increasing active problem solving and the skill in changing one’s view of a situation), we could prevent relapse and maintain recovery. This therefore has important implications for the psychological treatment of psychosis.”

Source: King’s College London