Tag: 26/1/22

Categories : AntibioticsTags :

Nanoparticle and Antibiotic Polytherapy Defeats AMR Bacteria

On By ModernMedia
Polytherapy with PMB and cubosomes result in interactions with the bacterial OM in two consecutive ways: PMB initially interacts with the outer leaflet of OM via electrostatic interactions, leading to destabilised areas. Cubosomes then contact with the bilayer, causing further membrane perturbations via a lipid-exchange process. Credit: Monash University/Lai et al.

Researchers from Monash University have discovered a potential new method to circumvent antibiotic resistance, by means of a nanoparticle and antibiotic polytherapy. This approach could also reduce antibiotic intake.

The World Health Organisation (WHO) has declared antimicrobial resistance (AMR) to be among the top 10 global public health threats. A recent report found that in 2019, 1.27 million deaths were directly attributable to AMR infections – more than deaths from either HIV or TB.

AMR occurs when pathogens evolve to no longer respond to medicines, consequently infections become increasingly difficult or impossible to treat.

The study, which appears in Nature Communications, has found that the use of nanoparticles in combination with other antibiotics, is an effective strategy to improve bacterial killing.

For Gram-negative bacteria, polymyxins have been used as drugs of last resort as they disrupt the bacterial outer membrane (OM), causing it to become more permeable, causing cell contents to leak out and kill the bacteria.

The strategy involves administering polymyxin B (PMB) alongside cube-shaped nanoparticles called cubosomes. The PMB disrupted the OM first, but not enough to kill the cell. When the accompanying cubosome bound to the OM, disrupting it further, successfully killing the cell. Interestingly, loading PMB into the cubosomes as a carrier had little effect; in fact, the cubosome strengthened the OM.

“This is a stunning finding in how we deliver medicine and how the medicine we take impacts us in the future,” said lead researcher Dr Hsin-Hui Shen. 

This approach also means that lower dosages of antibiotics could be used. “Instead of looking for new antibiotics to counteract superbugs, we can use the nanotechnology approach to reduce the dose of antibiotic intake, effectively killing multidrug-resistant organisms.”

It has been 30 years since the discovery of the last new antibiotic, and in coming years, the growing crisis of antibiotics resistance will result in increased mortality from basic infections because they have developed antimicrobial resistance.

Without effective antimicrobials, the WHO warns that the success of modern medicine in treating infections, including during major surgery and cancer chemotherapy, would be at increased risk.

While nanoparticles had been used for a long time before as antimicrobial carriers,  “but the use of nanoparticles in polytherapy treatments with antibiotics in order to overcome antimicrobial resistance has been overlooked,” explained Dr Shen. “The use of nanoparticles-antibiotics combination therapy could reduce the dose intake in the human body and overcome the multidrug resistance.”

Research will now progress to the testing phase.

Source: Monash University

Categories : Substance UseTags :

Many Youths with Substance Use Disorder Also Have Autism Traits

On By ModernMedia
Source: Andrew Neel on Unsplash

One in five teens and young adults seeking treatment for substance use may have traits characteristic of a previously unrecognised autism spectrum disorder (ASD), according to a study by researchers at Massachusetts General Hospital (MGH).

The study, published in The American Journal on Addictions, found that among patients with an average age of 18.7 years being treated in an outpatient substance use disorder (SUD) clinic, 20% had elevated scores on the Social Responsiveness Scale-2 (SRS-2), a parent- or teacher-reported measure that has been shown to reliably identify the presence and severity of social impairment among individuals along the autism spectrum, and to distinguish autism from other disorders.

Lead author James McKowen, PhD, said this is the first study examining the prevalence of autistic traits among young people with SUD.

“Usually studies of substance use disorder in autism are done in those with an autism diagnosis already,” he said. “We have looked at this question from the other side, asking how many people with substance use disorder have autism.”

The researchers asked parents of 69 youths reporting for the first time to a specialty outpatient psychiatric SUD clinic to fill out the SRS-2 form. The form is designed to measure an individual’s social awareness, cognition, communication and motivation, and restricted interests and repetitive behaviours.

Though few differences were found between those with elevated autistic trait scores and those with lower, non-autistic scores in terms of demographic or psychiatric factors, adolescents with higher SRS-2 scores had a nearly eightfold higher likelihood of stimulant use disorder, and a fivefold higher risk for opioid use disorder.

According to the researchers, the findings highlight the importance of assessing patients in a SUD treatment setting for autistic traits.

“For clinicians, the big takeaway point from this study is that we need to get better at screening and certainly training in the presence of autism spectrum disorder,” said Dr McKown. Clinicians treat the SUD “but don’t have specialty developmental training, particularly for issues around autism.”

The researchers are developing a free clinical therapy protocol that can help clinicians better address the issues of autistic traits in patients with SUD.

Source: Massachusetts General Hospital

Categories : CancerTags :

Coffee Consumption Lowers Endometrial Cancer Risk

On By ModernMedia
Photo by Mike Kenneally on Unsplash

Higher coffee consumption is linked with a lower risk of endometrial cancer, according to a new analysis which appears in the Journal of Obstetrics and Gynaecology Research. In addition, there was evidence that caffeinated coffee may provide better protection than decaffeinated coffee.

Risk factors for endometrial cancer include long-term exposure to excess oestrogen, obesity, nulliparity, diabetes mellitus, and hypertension, whereas protective factors include physical activity, aspirin intake, and certain dietary habits.

The analysis, which included 24 studies on coffee intake (12 case–control and 12 cohort studies), had 9833 new cases of endometrial cancer occurring in 699 234 individuals.

People in the highest category of coffee intake had a 29% lower relative risk of developing endometrial cancer than those in the lowest category. Additionally, women with a higher BMI or who smoked saw a greater benefit in risk reduction, though they still had a higher risk overall.

The authors of the analysis highlight several mechanisms that have been associated with the potential anti-cancer effects of coffee:

“Coffee contains many bioactive components, such as phenolic compounds. These polyphenols can increase the homocysteine concentrations in the plasma and inhibit DNA methylation in a dose-dependent manner, which prevents the downregulation of tumour suppressor proteins and DNA repair enzymes involved in carcinogenesis.”

They conclude that more studies with larger sample sizes are needed to better understand the effects of subgroups such as smoking status, as well as the benefits of coffee consumption in relation to endometrial cancer.

Source: Wiley

Categories : COVID Immune SystemTags :

Existing COVID Vaccines Trigger Lasting T Cell Response

On By ModernMedia
Image from Pixabay

Scientists have found that four COVID vaccines (Pfizer-BioNTech, Moderna, J&J/Janssen, and Novavax) prompt the body to make effective, long-lasting T cells against SARS-CoV-2. These T cells can recognise SARS-CoV-2 Variants of Concern, including Delta and Omicron.

The new study, published in Cell, showed that the vast majority of T cell responses are also still effective against Omicron, reducing the odds of illness for up to six months, regardless of vaccine.

These data come from adults who were fully vaccinated, but not yet boosted. The researchers are now investigating T cell responses in boosted individuals and people who have experienced “breakthrough” COVID cases.

The study also shows that fully vaccinated people have fewer memory B cells and neutralising antibodies against the Omicron variant. This finding is in line with initial reports of waning immunity from laboratories around the world.

Without enough neutralising antibodies, Omicron is more likely to cause a breakthrough infection, and fewer memory B cells means a slower production of more neutralising antibodies.

Co-first author Camila Coelho, PhD, said: “Our study revealed that the 15 mutations present in Omicron RBD can considerably reduce the binding capacity of memory B cells.”

Neutralising antibodies and memory B cells are only two arms of the body’s adaptive immune response. , T cells do not prevent infection, rather they patrol the body and destroy cells that are already infected, which prevents a virus from multiplying and causing severe disease.

The team believes the “second line of defence” from T cells helps explain Omicron’s reduced severity in vaccinated people. The variant also appears to infect different tissues.

To know whether the vaccine-induced T cells they detected in their study were actually effective against variants such as Delta and Omicron, the scientists took a close look at how the T cells responded to different viral “epitopes.”

Every virus is made up of proteins that form a certain shape or architecture. A viral epitope is a specific landmark on this architecture that T cells have been trained to recognise. Current COVID vaccines were designed to teach the immune system to recognise specific epitopes on the initial variant of SARS-CoV-2, specifically targeting the Spike protein which the virus uses to access human cells. As the virus has mutated, its architecture has changed, and the concern is that immune cells will no longer recognise their targets.

The new study shows that while the architecture of Omicron is different enough to evade some neutralising antibodies and memory B cells, memory T cells still do a good job of recognising their targets, even on the highly mutated Omicron variant. Overall, at least 83 percent of the CD4+ (helper) T cell responses and 85 percent of the CD8+ T cell responses stayed the same, no matter the vaccine or the variant.

The memory B cells that do bind Omicron are likely to also contribute to protection against severe disease, forming multiple lines of defence. 

Researchers are now focusing on measuring T cells, B cells and antibody responses after COVID booster shots, and also characterising immune responses after a breakthrough infection.

Source: La Jolla Institute

Categories : AgeingTags :

Two Key Proteins with a Major Role in Ageing

On By ModernMedia
Image by Mar Lezhava on Unsplash

In the largest genetic study of ageing to date, two key proteins have been identified that play a significant role in the ageing process. Developing drugs that target these proteins could be one way of slowing down ageing.

Genetics, lifestyle, environment and chance influence ageing. The study sheds light on the part proteins play in this process. Some people have higher or lower levels of certain proteins according to their individual DNA, which in turn affect a person’s health.

In a study published in Nature Aging, researchers from the University of Edinburgh combined the results of six large genetic studies into human ageing – each containing genetic information on hundreds of thousands of people.

Among 857 proteins studied, researchers identified two that had significant negative effects across various ageing measures.

People who inherited DNA that causes raised levels of these proteins were frailer, had poorer self-rated health and were less likely to live an exceptionally long life than those who did not.

The first protein, apolipoprotein(a) (LPA), is made in the liver and thought to play a role in clotting. High levels of LPA can increase the risk of atherosclerosis – a condition in which arteries become clogged with fatty substances. Heart disease and stroke is a possible outcome.

The second protein, vascular cell adhesion molecule 1 (VCAM1), is primarily found on the surfaces of endothelial cells lining blood vessels. The protein controls the vessels’ expansion and retraction – and have a function in blood clotting and the immune response.

Levels of VCAM1 increase in response to signals indicating an infection, and the protein then allows immune cells to cross the endothelial layer.

The researchers say that drugs used to treat diseases by reducing levels of LPA and VCAM1 could have the added benefit of improving quality and length of life.  

One such example is a clinical trial that is testing a drug to lower LPA as a way of reducing the risk of heart disease. No clinical trials with VCAM1 are underway, but studies in mice have shown how antibodies lowering this protein’s level improved cognition during old age.

The identification of these two key proteins could help extend the healthy years of life. Drugs that reduce these protein levels in the blood could allow the average person to live as healthy and as long as individuals who have won the genetic lottery and are born with genetically low LPA and VCAM1 levels.

Source: University of Edinburgh