Study identifies specific antioxidants that may reduce oncogenic HPV infection in women
Louisiana State University, April 12, 2021
A study led by Hui-Yi Lin, Ph.D., Professor of Biostatistics, and a team of researchers at LSU Health New Orleans Schools of Public Health and Medicine has found that adequate levels of five antioxidants may reduce infection with the strains of the human papillomavirus (HPV) associated with cervical cancer development. Findings are published in the Journal of Infectious Diseases. Although previous studies have suggested that the onset of HPV-related cancer development may be activated by oxidative stress, the association had not been clearly understood. This study evaluated associations between 15 antioxidants and vaginal HPV infection status — no, low-risk, and oncogenic/high-risk HPV (HR-HPV) — in 11,070 women aged 18-59 who participated in the 2003-2016 National Health and Nutrition Examination Survey.
Study results showed that lower levels of serum albumin and four dietary antioxidants – vitamins A, B2, E, and folate — were associated with a higher risk of HR-HPV infection. Albumin is the most bountiful circulating protein in plasma, and decreased serum albumin was found to be associated with increased systemic inflammation and impaired immune response. Based on the four dietary antioxidants, the researchers developed a nutritional antioxidant score.
“Our results showed that the women with the lowest quartile of the nutritional antioxidant score had a higher chance of both high-risk and low-risk HPV infection compared with the women with the highest quartile score after adjusting for other factors such as age, race, smoking, alcohol, and the number of sexual partners in past 12 months,” notes the paper’s lead author Hui-Yi Lin, PhD, Professor of Biostatistics at LSU Health New Orleans School of Public Health.
Human Papillomavirus is a well-known risk factor for cervical cancer, which is the fourth most common female cancer and contributed to 7.5% of cancer deaths for women worldwide in 2018. Certain HPV strains are more likely to trigger precursor events leading to cancer development. These strains are called oncogenic or high-risk [HR] HPV strains. Almost all cervical cancers are directly linked to previous infection with one or more HR-HPV infections.
“Currently, there is no effective antiviral therapy to clear genital HPV infection,” adds Dr. Lin. “It is important to identify modifiable factors, such as antioxidants, associated with oncogenic HPV infection in order to prevent HPV carcinogenesis onset.”
Exercise benefit in breast cancer linked to improved immune responses
Tumors grew more slowly and responded better to immunotherapy in mice that exercised compared with sedentary mice.
Massachusetts General Hospital, April 12, 2021
Exercise training may slow tumor growth and improve outcomes for females with breast cancer – especially those treated with immunotherapy drugs – by stimulating naturally occurring immune mechanisms, researchers at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) have found.
Tumors in mouse models of human breast cancer grew more slowly in mice put through their paces in a structured aerobic exercise program than in sedentary mice, and the tumors in exercised mice exhibited an increased anti-tumor immune response.
“The most exciting finding was that exercise training brought into tumors immune cells capable of killing cancer cells known as cytotoxic T lymphocytes (CD8+ T cells) and activated them. With more of these cells, tumors grew more slowly in mice that performed exercise training,” says co-corresponding author Dai Fukumura, MD, PhD, deputy director of the Edwin L. Steele Laboratories in the Department of Radiation Oncology at MGH.
As Fukumura and colleagues report in the journal Cancer Immunology Research , the beneficial effects of exercise training are dependent on CD8+ T cells; when the researchers depleted these cells in mice, tumors in mice that exercised no longer grew at a slower rate.
They also found evidence that recruitment of CD8+ T cells to tumors was dependent on two chemical recruiters (chemokines) labeled CXCL9 and CXCL11. Levels of these chemokines were increased in mice that exercised, and mice that were genetically engineered to lack the receptor (docking site) for these chemokines did not recruit CD8+ T cells and did not have an anti-tumor benefit.
“Humans whose tumors have higher levels of CD8+ T cells tend to have a better prognosis, respond better to treatment, and have reduced risk of cancer recurrence compared with patients whose tumors have lower levels of the immune cells, effects that were echoed by a reduced incidence of metastasis, or spread, of the cancers in mice that exercised,” says co-corresponding author Rakesh K. Jain, PhD, director of the Steele Labs at MGH and Andrew Werk Cook Professor of Radiation Oncology at HMS.
CD8+ T cells are also essential for the success of drugs known as immune checkpoint inhibitors, such as Keytruda (pembrolizumab), Opdivo (nivolumab) and Yervoy (ipilimumab), which have revolutionized therapy for many types of cancer, but have to date had only limited success in breast cancer. The researchers found that exercise-trained mice displayed a much better response to immune checkpoint blockade, while the drugs did not work at all in sedentary mice.
“We showed that daily sessions of a moderate-to-vigorous intensity, continuous aerobic exercise training, lasting 30-45 minutes per session, induces a profound reprogramming of the tumor microenvironment that rewires tumor immunity, recruiting and activating CD8+ T cells to an unprecedented level with a non-pharmacological approach. Similar exercise training could be prescribed to a patient referred to an exercise oncology program,” says Igor L. Gomes-Santos, PhD, lead author and exercise physiologist and post-doctoral fellow in the Steele Labs.
He notes that current clinical guidelines focus on general wellness, improved fitness levels and quality of life, but not necessarily on improved cancer treatment, especially immunotherapy, and that this lack of evidence limits its application in clinical practice.
More convincing, mechanism-based data are needed to motivate oncologists to discuss exercise training with their patients, to motivate patients to become more active and to expand implementation of outpatient exercise oncology programs, the investigators say.
Higher dietary total antioxidant capacity associated with lower risk of cognitive impairment
National University of Singapore, April 12 2021.
The study included 16,703 participants in the Singapore Chinese Health Study, which enrolled men and women aged 45 to 74 years between April 1993 and December 1998. Questionnaires completed upon enrollment provided information concerning dietary and supplement intake that was evaluated for antioxidant content using the Comprehensive Dietary Antioxidant Index and the Vitamin C Equivalent Antioxidant Capacity. Disease status and lifestyle factors were updated during follow-up visits conducted every five to six years. Cognitive function was evaluated 20.2 years after the beginning of the study.
Cognitive impairment was detected among 14.3% of the participants. Among those whose Comprehensive Dietary Antioxidant Index Scores placed them among the top 25% of participants, the risk of having developed cognitive impairment was 16% lower than that of participants among the lowest 25%. Those whose Vitamin C Equivalent Antioxidant Capacity was among the top 25% experienced a risk that was 25% lower. When antioxidant nutrients were individually analyzed, greater daily intake of vitamin C, vitamin E, carotenoids and flavonoids was associated with a reduction in the risk of cognitive impairment. Among carotenoids, alpha carotene and beta cryptoxanthin were found to be protective and among flavonoids, anthocyanins, flavan-3-ols, flavones and flavonols were associated with lower risk.
“These findings suggested that higher total antioxidant capacity of midlife diet was associated with lower odds of cognitive impairment in later life,” authors Li-Ting Sheng and colleagues concluded. “The generalizability of results to other populations remains to be confirmed, and future studies with repeated measures of dietary variables and cognitive functions are still needed.
Beneficial effect of quercetin on ovalbumin-induced rhinitis
Xian Jiao-tong University (China), April 8, 2021
According to news reporting originating in Shaanxi, People’s Republic of China, research stated, “Asthma is a chronic inflammatory airway disease, characterized by reversible goblet cells, smooth muscle hyperplasia, airflow obstruction, hyperactivity enhanced, ultra-structural remodeling, and airway mucus production. The current experimental study was aimed at scrutinizing quercetin’s inhibitory effect on airway inflammation in mice and its possible mechanism of action.”
The news reporters obtained a quote from the research from Xi’an Jiaotong University, “The mice received varying doses of quercetin from 22-30 days (1, 10 and 50 mg / kg, p.o.) and montelukast (10 mg / kg, p.o.). Intranasal OVA has been instilled on the 21 days. Biochemical parameters, spleen weight, physiological parameters, interleukin (IL-113 and IL-6) parameters and immunoglobin-E (IgE) were calculated at the end of the experimental study. To investigate the potential mechanism of action, Paw edema and mast cell de granulation are estimated. Used to measure immune and inflammatory mediators, qRT-PCR technique. Quercetin significantly (P <0.001) reduced IgE levels in the asthma mice serum. Inflammatory cells in the mice BALF are significantly reduced in a dose-dependent manner through quercetin. Quercetin (P <0.05) significantly reduced the level of TNF-alpha, IL-1 beta, IL-4 and IL-5 cytokines and increased the level of IFN-pi in allergic asthma mice caused by OVA. In contrast, there was no significant effect in the body weight of mice treated with quercetin.”
According to the news reporters, the research concluded: “Based on the result, we may infer that quercetin demonstrates an inflammatory mechanism for the therapeutic effect of inflammation in allergic asthma.”
This research has been peer-reviewed.
Fighting dementia with play
ETZ Zurich (Switzerland), April 9, 2021
A dementia diagnosis turns the world upside down, not only for the person affected but also for their relatives, as brain function gradually declines. Those affected lose their ability to plan, remember things or behave appropriately. At the same time, their motor skills also deteriorate. Ultimately, dementia patients are no longer able to handle daily life alone and need comprehensive care. In Switzerland alone, more than 150,000 people share this fate, and each year a further 30,000 new cases are diagnosed.
To date, all attempts to find a drug to cure this disease have failed. Dementia, including Alzheimer’s – the most common of several forms of dementia – remains incurable. However, a clinical study carried out in Belgium with the involvement of ETH researcher Eling de Bruin has now shown for the first time that cognitive motor training improves both the cognitive and physical skills of significantly impaired dementia patients. A fitness game, known as “Exergame”, developed by the ETH spin-off Dividat was used in the study.
Better cognitive ability thanks to training
In 2015, a team of scientists led by ETH researcher Patrick Eggenberger showed that older people who train both body and mind simultaneously demonstrate better cognitive performance and can thereby also prevent cognitive impairment (as reported by ETH News). However, this study was carried out on healthy subjects only.
“It has been suspected for some time that physical and cognitive training also have a positive effect on dementia,” explains de Bruin, who worked with Eggenberger at the Institute of Human Movement Sciences and Sport at ETH Zurich. “However, in the past it has been difficult to motivate dementia patients to undertake physical activity over extended periods.”
ETH spin-off combines exercise and fun
With a view to changing this, Eva van het Reve, a former ETH doctoral student, founded the ETH spin-off Dividat in 2013 together with her PhD supervisor Eling de Bruin and another doctoral student. “We wanted to devise a customised training programme that would improve the lives of older people,” says van het Reve. Fun exercises were developed in order to encourage people who were already experiencing physical and cognitive impairments to participate in training, and the Senso training platform was born.
The platform consists of a screen with the game software and a floor panel with four fields that measure steps, weight displacement and balance. The users attempt to complete a sequence of movements with their feet as indicated on the screen, enabling them to train both physical movement and cognitive function simultaneously. The fact that the fitness game is also fun makes it easier to motivate the subjects to practice regularly.
Eight weeks’ training for dementia patients
An international team led by Nathalie Swinnen, a doctoral student at KU Leuven, and co-supervised by ETH researcher de Bruin, recruited 45 subjects for the study. The subjects were residents of two Belgian care homes, aged 85 years on average at the time of the study and all with severe dementia symptoms.
“The participants were divided into two groups on a random basis,” explains de Bruin. “The first group trained for 15 minutes with the Dividat Senso three times a week for eight weeks, while the second group listened to and watched music videos of their choice.” Following the eight-week training programme, the physical, cognitive and mental capacity of all subjects was measured in comparison with the start of the study.
Regular play has an effect
The results offer hope to dementia patients and their relatives: training with this machine indeed enhanced cognitive skills, such as attention, concentration, memory and orientation. “For the first time, there’s hope that through targeted play we will be able not only to delay but also weaken the symptoms of dementia,” emphasises de Bruin.
It is particularly striking that the control group deteriorated further over the eight-week period, while significant improvements were recorded in the training group. “These highly encouraging results are in line with the expectation that dementia patients are more likely to deteriorate without training,” adds de Bruin.
But playful training not only has a positive impact on cognitive ability – researchers were also able to measure positive effects on physical capability, such as reaction time. After just eight weeks, the subjects in the training group reacted significantly more quickly, while the control group deteriorated. This is encouraging in that the speed with which older people respond to impulses is critical in determining whether they can to avoid a fall.
A better understanding of brain processes
The research group led by de Bruin is currently working on replicating the results of this pilot study with people with mild cognitive impairment – a precursor of dementia. The aim is to use MRI scans to investigate more closely the neural processes in the brain responsible for the cognitive and physical improvement.
Maple syrup protects neurons and nurtures young minds
University of Montreal (Quebec), April 13, 2021
Catherine Aaron and Gabrielle Beaudry were 17 when they knocked on the door of the laboratory of Alex Parker, a neuroscience researcher at the University of Montreal Hospital Research Centre (CRCHUM). While students at Collège Jean-de-Brébeuf in Montreal, they were looking for a mentor for an after-school research project. Two and half years later, the results of this scientific adventure were published in the Journal of Agricultural and Food Chemistry.
“We wanted to test the effect of a natural product on a neurodegenerative disease such as Alzheimer’s. Professor Parker had already discovered that sugar prevents the occurrence of amyotrophic lateral sclerosis (ALS) in an animal model of the disease, the C. elegans worm. That’s how we got the idea of maple syrup, a natural sugar produced in Quebec,” said Beaudry.
Supervised by PhD student Martine Therrien and Alex Parker, Aaron and Beaudry added maple syrup to the diet of these barely 1 mm-long nematodes. “We just gave them a supplement of maple syrup at various concentrations and compared with a control group that had a normal diet,” said Aaron. “After twelve days, we counted under the microscope the worms that were moving and those that were paralyzed. The worms that had consumed the highest dose of syrup were much less likely to be paralyzed.”
Alex Parker’s C. elegans worms are genetically modified to express a protein involved in ALS in motor neurons – TDP-43. “When they are adults, around 12 days, their motor neurons break down. Normally, at two weeks of life, 50% of the worms are completely paralyzed. But among those that received a diet enriched with 4% maple syrup, only 17% were paralyzed. We can therefore conclude that maple syrup protects neurons and prevents the development of amyotrophic lateral sclerosis in C. elegans worms,” said Parker, a researcher at the CRCHUM and professor at the Faculty of Medicine, University of Montreal.
How can we explain this dramatic effect? “Sugar is good for the nervous system. Diseased neurons require more energy to combat toxic proteins. But maple syrup is rich in polyphenols, powerful antioxidants found in certain foods. We isolated phenols contained in the maple syrup, and we showed that two polyphenols in particular, gallic acid and catechol, have a neuroprotective effect. In pure maple syrup, these polyphenols are found in low concentrations. Probably a combination of sugar and polyphenols prevents the occurrence of the disease in worms,” said Therrien, a PhD student at the CRCHUM.
But don’t go ahead and gorge yourself on maple syrup thinking it’ll protect you against neurological diseases! “The life expectancy of C. elegans worms is only three weeks. They are spared the long-term toxic effects of sugar. Humans who consume comparable amounts of sugar risk developing chronic diseases such Type 2 diabetes and obesity,” cautioned Parker.
Amyotrophic lateral sclerosis is a rare neuromuscular disease that causes paralysis and death a few years after the onset of symptoms. So far, no cure is available for patients. This latest study on maple syrup and the C. elegans worm was conducted for educational purposes. Other studies by Alex Parker with C. elegans have led to the discovery of promising drugs, which will be tested in patients in a few years.
Profound loss of pleasure related to early-onset dementia
University of Sydney, April 12, 2021
– Loss of pleasure has been revealed as a key feature in early-onset dementia (FTD), in contrast to Alzheimer’s disease.- Scans showed grey matter deterioration in the so-called pleasure system of the brain.
– These regions were distinct from those implicated in depression or apathy – suggesting a possible treatment target.
People with early-onset dementia are often mistaken for having depression and now Australian research has discovered the cause: a profound loss of ability to experience pleasure – for example a delicious meal or beautiful sunset – related to degeneration of ‘hedonic hotspots’ in the brain where pleasure mechanisms are concentrated.
The University of Sydney-led research revealed marked degeneration, or atrophy, in frontal and striatal areas of the brain related to diminished reward-seeking, in patients with frontotemporal dementia (FTD).
The researchers believe it is the first study to demonstrate profound anhedonia – the clinical definition for a loss of ability to experience pleasure – in people with FTD.
Anhedonia is also common in people with depression, bipolar disorder and obsessive-compulsive disorder and can be particularly disabling for the individual.
In the study, patients with FTD – which generally affects people aged 40-65 – displayed a dramatic decline from pre-disease onset, in contrast to patients with Alzheimer’s disease, who were not found to show clinically significant anhedonia.
The results point to the importance of considering anhedonia as a primary presenting feature of FTD, where researchers found neural drivers in areas that are distinct from apathy or depression.
The findings were published today in the leading neuroscience journal, Brain.
The paper’s senior author, Professor Muireann Irish from the University of Sydney’s Brain and Mind Centre and School of Psychology in the Faculty of Science, said despite increasing evidence of motivational disturbances, no study had previously explored the capacity to experience pleasure in people with FTD.
“Much of human experience is motivated by the drive to experience pleasure but we often take this capacity for granted.
“But consider what it might be like to lose the capacity to enjoy the simple pleasures of life – this has stark implications for the wellbeing of people affected by these neurodegenerative disorders.
“Our findings also reflect the workings of a complex network of regions in the brain, signaling potential treatments,” said Professor Irish, who also recently published a paper in Brain about moral reasoning in FTD.
“Future studies will be essential to address the impact of anhedonia on everyday activities, and to inform the development of targeted interventions to improve quality of life in patients and their families.”