Day: May 7, 2021

Categories : CancerTags :

Fooling Cancer Cells into Taking in Anti-cancer Drugs

On By ModernMedia
Stress Fibres and Microtubules in Human Breast Cancer Cells. Photo by National Cancer Institute on Unsplash

Attaching anti-cancer drugs to a common protein and making a ‘poison pill’ that cancer cells take in could increase the effectiveness of chemotherapy, according to researchers at Massachusetts General Hospital (MGH).

In order to kill cancer cells effectively, enough anticancer drugs need to be delivered into a tumour as possible, which is often difficult. A new approach involves binding the drugs to albumin, the most abundant protein in blood. Tumours have a strong appetite for protein nutrients to fuel malignant growth. When they consume albumin, the tumour will also take in the drugs bound to this protein.

One commonly used albumin-bound drug is nanoparticle albumin-bound paclitaxel (nab-PTX), which has been successfully used in the treatment of advanced lung and pancreatic cancers. “Not all patients respond to nab-PTX, though, and the effectiveness of its delivery to tumours has been mixed, owing to an incomplete understanding of how albumin impacts drug delivery and actions,” said senior author Miles Miller, PhD, a principal investigator in the MGH Center for Systems Biology and assistant professor of Radiology at Harvard Medical School.

To improve their understanding, Prof Miller and colleagues examined the delivery of nab-PTX to tumours at a single-cell resolution in mouse models of cancer. Using 3D microscopy and tissue clearing technology, the team found that cancer cells can take up a significant amount of nab-PTX. They also found that the consumption of these drugs is controlled by signaling pathways involved in the cells’ uptake of nutrients such as albumin.

“This discovery suggested that if we could manipulate these pathways, we might be able to trick cancer cells into a nutrient-starved state, thereby enhancing their consumption of nab-PTX,” explained Ran Li, PhD, first author on the study and an instructor in the MGH Department of Radiology and the Center for Systems Biology. Indeed, treating tumours with an inhibitor of insulin-like growth factor 1 receptor, an important component of one of the signaling pathways, improved the accumulation of nab-PTX in tumours and boosted its effectiveness.

“These results offer new possibilities to improve delivery of albumin-bound drugs in patients with diverse types of cancer,” said Prof Miller.

Source: Phys.Org

Journal information: Ran Li et al, Therapeutically reprogrammed nutrient signalling enhances nanoparticulate albumin bound drug uptake and efficacy in KRAS-mutant cancer, Nature Nanotechnology (2021). DOI: 10.1038/s41565-021-00897-1

Categories : Immune SystemTags :

Tropical Ginger Can Block Inflammation

On By ModernMedia
A piece of ginger. Photo by Lawrence Aritao on Unsplash

New research has shown how compound found in the tropical ginger plant, 1′-acetoxychavicol acetate, or ACA, can have an anti-inflammatory effect.

Researchers found that ACA reduces mitochondrial damage by lowering levels of mitochondrial reactive oxygen species (ROS), blocking activation of a crucial protein complex known as the NLRP3 inflammasome. A number of inflammatory diseases, like inflammatory bowel disease, display improper and chronic activation of this complex.

It has been suggested by previous studies that the NLRP3 inflammasome plays a significant role in promoting inflammation by secreting a molecule called IL-1β. This molecule works as a messenger, sending various immune cells to the site of injury or infection. Further studies detailed how production of ROS can help to trigger the NLRP3 inflammasome. Because other groups showed that the ginger compound ACA can reduce ROS production in certain immune cells, the researchers wondered how this compound would affect the way NLRP3 inflammasome worked.

“Many disease pathogeneses involve dysregulation of the inflammasome,” commented Daisuke Ori, co-lead author on the study. “Blood cells from people suffering from rheumatoid arthritis or other autoimmune disorders frequently have increased levels of inflammasome-derived IL-1β. Therefore, targeting the NLRP3 inflammasome with a compound like ACA may be a promising therapeutic strategy.”

The researchers took immune cells from mouse bone marrow, and also used a mouse model of colitis. ACA was added to the growing cells and the compound was added to their mice’s food. The researchers then looked at the effects on ROS production, secretion of IL-1β, and other markers of inflammation.

“Cells treated with ACA had significantly reduced IL-1β production, as well as lower levels of ROS,” explained senior author Taro Kawai. “ACA could also inhibit NLRP3 inflammasome activation in the colitis mouse model.” These in vivo results are promising, as they suggest ACA has the potential to treat or prevent the development of inflammatory diseases. “Interestingly, we did not observe high levels of immune cell death when using ACA, which means that it may be relatively safe,” continued Ori.

The study provided novel evidence for a specific molecular mechanism governing the previously observed anti-inflammatory properties of ACA. The study also showed the potential of ACA for therapeutic use in diseases mediated by IL-1β molecules, or associated with cytokine storms, as seen in patients suffering from severe COVID.

Source: Medical Xpress

Journal information: Sophia P M Sok et al. 1′-acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression, International Immunology (2021). DOI: 10.1093/intimm/dxab016

Categories : Substance UseTags :

Cannabis Vaping Soared in High School Students Before COVID

On By ModernMedia
Man vaping. Photo by Nery Zarate on Unsplash

With reports of severe lung illnesses related to vaping making headlines in 2019, cannabis use skyrocketed among high school students were soaring.

Cannabis vaping involves inhaling evaporated oils, or vapours from heated concentrates known as dabs. Joseph J Palamar, PhD, of New York University reported on his study in the Journal of Adolescent Health.

The long-running Monitoring the Future study results showed that 4.9% (95% CI 4.3%-5.5%) of high school students reported “frequent” vaping of cannabis products — 10 times or more in the previous month — up from 2.1% in 2018 (95% CI 1.7%-2.6%). Rates of any cannabis vaping in the previous month also rose significantly, from 7.5% in 2018 (95% CI 6.7%-8.4%) to 14.0% in 2019 (95% CI 13.1%-14.9%).

These increases accompanied an unsettling outbreak of respiratory illnesses, until it was eclipsed by the COVID pandemic. Nearly 3000 Americans, mostly young adults, fell ill with EVALI — e-cigarette or vaping-associated lung injury — and 68 died, noted Dr Palamar. Epidemiological and lab research eventually identified vitamin E acetate as the likely cause. The substance is a common component of illicit cannabis vaping products, even though a substantial minority of victims denied use of such products.

Dr Palamar’s study drew on Monitoring the Future data on 4072 students in 10th and 12th grades in 2018 and 8314 in 2019. The study also highlighted other trends.

Cannabis vaping in the past month nearly tripled among female students from 2018 to 2019, while rates for students in general age 18 and older rose 2.5-fold. Social activity, as indicated by reports of “going out” four to seven times a week, was linked to increased rates of cannabis vaping. There were also small increases in cannabis vaping among students reporting other psychoactive drug use including opioids, cocaine, “tranquilisers”, and non-LSD hallucinogens.

The study did not address the extent to which school closures and social restrictions resulting from the COVID pandemic affected these trends, and it will be some before data from Monitoring the Future can answer this as the survey was stopped in March 2020 when the pandemic closed schools.

Nevertheless, the available 2020 data showed that the number of 10th graders saying cannabis was “fairly easy” or “very easy” to obtain had dropped sharply, accelerating a trend underway for more than 20 years. This was despite the spread of legal marijuana.

Dr Palamar noted several limitations to his study and to Monitoring the Future in general. Data on drug use was self-reported, and the survey took place at schools, meaning that students “chronically absent or who dropped out are underrepresented,” he wrote. There were also some subgroups such as those vaping cannabis daily, that were too small for analysis.

Source: MedPage Today

Journal information: Palamar J “Increases in frequent vaping of cannabis among high school seniors in the United States, 2018-2019” J Adolesc Health 2021; DOI: 10.1016/j.jadohealth.2021.03.034.

Categories : VaccinesTags :

Zapping Pathogens for Faster, Cheaper Vaccine Production

On By ModernMedia
Photo by Zoltan Tasi on Unsplash

A team of researchers from three Fraunhofer Institutes has developed a method of producing vaccines that is faster, more efficient and more environmentally friendly than the conventional production process.

Vaccines date back to 1796, and the first vaccines were simply pus samples freshly taken from people with cowpox. Gruesomely, the Spanish shipped orphaned children to South America to act as cowpox carriers — the world’s first vaccine shipment. As medicine advanced, scientists were able to isolate viruses and inactivate them. However, this is still a lengthy, expensive process.  

But a new production process for inactivated vaccines is set to make vaccine production faster, more environmentally friendly and more efficient than ever before while also reducing costs. Dr Sebastian Ulbert and Dr Jasmin Fertey from the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig, Frank-Holm Rögner from the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP in Dresden, and Martin Thoma from the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart have been awarded the 2021 Fraunhofer Prize for “Human- and Environment-Centered Technology” on behalf of their teams. 

To date, chemicals have always been used in inactivated vaccine production. The pathogens are stored with toxic chemicals, particularly formaldehyde, until the viral genetic information is completely destroyed and it is incapable of replication. This process is known as inactivation.
However, it has a number of drawbacks. For a start, the chemicals also destroy part of the external structures that the immune system forms antibodies from. Also, industrial-scale vaccine production involves large quantities of toxic chemicals, which are hazardous to humans and the environment. Finally, depending on the virus, it can take weeks to months to actually ‘kill’ it.

Their high-tech approach has none of these disadvantages. “Instead of inactivating the virus with toxic chemicals, we fire electrons at it,” explained Dr Ulbert. “The viral particle [is] almost completely intact. There are no chemicals that we need to dispose of and the entire process takes just a few seconds.” 

But there was a problem. The electrons can only penetrate liquids to less than half a millimetre, losing energy along the way. To reliably kill viruses in the liquid with the electrons, the liquid film has to be no thicker than around 0.1 millimetres—and it must be transported evenly, too. “This required complex equipment technology, which is why we brought Fraunhofer IPA on board,” said Rögner.

At Fraunhofer IPA, Martin Thoma developed two ways to overcome the problem. “The pouch module is suitable for conducting preliminary tests that provide useful information, while the tumbler module is beneficial for larger quantities,” said the physics graduate. On the basis of this setup, Dr Fertey investigated viruses such as influenza, Zika and herpes as well as numerous bacteria and parasites, which were treated with electrons subject to targeted acceleration via the pouch and tumbler module. “We were able to successfully and reliably inactivate all classes of pathogens,” said the delighted biologist.

In about five to seven years, the production modules—which are the size of a refrigerator—could be integrated into pharmaceutical production in order to produce vaccines in a quick, efficient and environmentally friendly process.

Source: Phys.Org

Categories : AgeingTags :

Older People That Feel Younger Live Longer

On By ModernMedia
A smiling elderly woman. Photo by Loren Joseph on Unsplash

A new study has found that older people who feel younger are generally more healthy. Such people have greater sense of well-being, better cognitive functioning, less inflammation, lower risk of hospitalisation and even live longer than their older-feeling peers. 

As Francis Bacon once said, “I will never be an old man. To me, old age is always 15 years older than I am.” Studies have shown that feeling younger than one’s chronological age has been known to have some health benefits. A twin study in Denmark showed that perceived age, correlated significantly with physical and cognitive functioning as well as with leucocyte telomere length — which prevents cells from becoming unable to divide.

Researchers from the German Centre of Gerontology analysed three years of data from 5039 participants in the German Ageing Survey, a longitudinal survey of German residents of age 40 and older. The survey had questions about the amount of perceived stress in peoples’ lives and their functional health—how well they could conduct daily activities such as dressing and walking. Participants also indicated their subjective age by answering the question, “How old do you feel?”

Participants with more reported stress tended to have a more rapid decline in functional health over three years, and that association between stress and functional health decline was stronger for chronologically older participants.

Among people who felt younger than their chronological age, there was a weaker association between stress and functional health decline. This protective effect was strongest among the oldest participants.

“Generally, we know that functional health declines with advancing age, but we also know that these age-related functional health trajectories are remarkably varied. As a result, some individuals enter old age and very old age with quite good and intact health resources, whereas others experience a pronounced decline in functional health, which might even result in need for long-term care,” said lead author Markus Wettstein, PhD, who is now at University of Heidelberg. “Our findings support the role of stress as a risk factor for functional health decline, particularly among older individuals, as well as the health-supporting and stress-buffering role of a younger subjective age.”

The researchers said their findings suggest that helping older people feel younger could mitigate the negative effects stress and improving health—though further study is needed to help determine what kind of interventions would work best. Dr Wettstein gave examples of such efforts, such as messaging campaigns to counteract ageism and negative age stereotypes and to promote ageing in a positive light could help people feel younger. More general stress-reduction interventions and stress management training could also prevent functional health loss among older adults.

Dr Wettstein said that there needs to be further studies to find the ideal gap between subjective and chronological age, as previous research has suggested that, up to a point, it’s helpful to feel younger, but those benefits decrease as the gap between subjective and chronological age increases. “Feeling younger to some extent might be adaptive for functional health outcomes, whereas ‘feeling too young’ might be less adaptive or even maladaptive,” he said.

Source: Medical Xpress

Journal information: Markus Wettstein et al, Feeling younger as a stress buffer: Subjective age moderates the effect of perceived stress on change in functional health., Psychology and Aging (2021). DOI: 10.1037/pag0000608