Tag: 24/7/23

Categories : Immune SystemTags : Leave a comment

Elevated Body Temperature Helps Gut Microbiota to Fight Viruses

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Researchers from The University of Tokyo have helped unravel the connection between high body temperature and increased viral resistance. Older adults are at a higher risk of contracting viral infections, research shows. Quite notably, they also have lower mean body temperatures – yet the effects of increased body temperature on fighting viral infections remain largely unexplored. The researchers found that higher temperature increased bile acids along with the infection-fighting capability of the gut microbiota. Their study was published in Nature Communications.

To conduct their experiments, the team used mice which were heat- or cold-exposed at 4°C, 22°C, or 36°C a week before influenza virus infection. After the viral infection was induced, the cold-exposed mice mostly died due to severe hypothermia, whereas the heat-exposed mice were highly resistant to the infection even at increasing doses of the virus. “High-heat-exposed mice raise their basal body temperature above 38°C, allowing them to produce more bile acids in a gut microbiota-dependent manner,” remarks Dr Takeshi Ichinohe from the Division of Viral Infection, The University of Tokyo, Japan.

The authors speculated that signalling of deoxycholic acid (DCA) from the gut microbiota and its plasma membrane-bound receptor “Takeda G-protein-coupled receptor 5” (TGR5) increased host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage.

While working on these experiments, the team noticed that mice infected with the influenza virus showed decreased body temperatures nearly four days after the onset of the infection, and they snuggled together to stay warm!

The team noticed similar results after switching the influenza virus with SARS-CoV-2 and the study results were also validated using a Syrian hamster model. Their experiments revealed that body temperature over 38°C could increase host resistance to influenza virus and SARS-CoV-2 infections. Moreover, they also found that such increase in body temperature catalyzed key gut microbial reactions, which in turn, led to the production of secondary bile acids. These acids can modulate immune responses and safeguard the host against viral infections.

Dr. Ichinohe explains, “The DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group.”

The team then performed extensive analysis to gain insight into the precise mechanisms underlying the gut-metabolite-mediated host resistance to viral infections in heat-exposed rodents. Besides, they also established the role of secondary bile acids and bile acid receptors in mitigating viral infections.

“Our finding that reduction of certain bile acids in the plasma of patients with moderate I/II COVID-19 may provide insight into the variability in clinical disease manifestation in humans and enable approaches for mitigating COVID-19 outcomes,” concludes Dr. Ichinohe.

To briefly summarize, the published study reveals that the high-body-temperature-dependent activation of gut microbiota boosts the serum and intestinal levels of bile acids. This suppresses virus replication and inflammatory responses that follow influenza and SARS-CoV-2 infections.

A heartfelt appreciation to the Japanese researchers for placing their trust in their intuition and gut instincts!

Source: University of Tokyo

Categories : COVIDTags : Leave a comment

Cognitive Impairment Persists Two Years after COVID Infection

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Image by Fusion Medical on Unsplash

Researchers from King’s College London have found that people with longer-term COVID symptoms including brain fog showed reduced performance in tasks testing different mental processes – up to two years after infection with the virus, according to results published in the journal eClinicalMedicine.

Researchers examined whether COVID infection affected performance in two rounds of online cognitive testing that took place in 2021 and 2022. Data was collected for over 3000 participants of the COVID Symptom Study Biobank study, across 12 tasks that tested memory, attention, reasoning, processing speed and motor control.

The participants whose test scores were most affected by COVID were those who had experienced symptoms related to the virus for 12 weeks or more. In these people, the effect of COVID on test accuracy was comparable in size to the effect of a 10-year increase in age.

There was no significant improvement in these test scores between the two rounds of testing, which took place nine months apart. By the second round of testing, the average time since participants’ initial COVID infection was almost two years.

The researchers then separated participants by whether they felt fully recovered following COVID infection. People who felt fully recovered after COVID infection performed similarly to those who had not had the virus at all. In contrast, participants who did not feel fully recovered after infection had lower task accuracy scores on average.

Lead author Dr Nathan Cheetham, a Senior Postdoctoral Data Scientist at King’s College London said:

“Our findings suggest that, for people who were living with long-term symptoms after having COVID, the effects of the coronavirus on mental processes such as the ability to recall words and shapes are still detectable at an average of almost two years since their initial infection.

“However, the result that COVID had no effect on performance in our tests for people who felt fully recovered, even if they’d had symptoms for several months and could be considered as experiencing ‘long COVID’, was good news. This study shows the need to monitor those people whose brain function is most affected by COVID-19, to see how their cognitive symptoms continue to develop and provide support towards recovery.”

Professor Claire Steves, a Professor of Ageing and Health at King’s College London, added:

“We used sensitive tests to measure speed and accuracy across a range of brain challenges. This study shows that some individuals have measurable changes in these tests after COVID-19 going on for nearly two years. The fact remains that two years on from their first infection, some people don’t feel fully recovered and their lives continue to be impacted by the long-term effects of the coronavirus. We need more work to understand why this is the case and what can be done to help.”

Source: King’s College London

Categories : CancerTags : Leave a comment

Scientists Create Protein that Blocks Breast Cancer Metastasis

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In a paper published in the journal Biomolecules, UK and Chinese researchers report their creation of a biomedical compound that has the potential to stop breast cancer metastasis.

The scientists from the Chemistry and Biochemistry Departments at the University of Liverpool and Nanjing Medical School in China have discovered a possible way to block proteins produced by cancer cells that promote metastasis – the chief impediment to successful cancer treatment.

Prof Philip Rudland from the University of Liverpool explained: “As a general rule, cancer that has spread is treated with chemotherapy, but this treatment can rarely be given without severely harming or becoming toxic to the patient. The importance of our work was to identify a specific and important target to attack, without toxic side effects.”

The University’s research team have in the past discovered that specific proteins are involved in the metastatic process; these proteins are different from those involved in the production of the primary tumour. One such example is a protein called ‘S100A4’, and is the protein chosen by the research team to target for the identification of chemical inhibitors of metastasis, using model systems of cells from the highly metastatic and incurable hormone receptor-free breast cancer.

Using these model systems, researchers at the University’s Department of Biochemistry discovered a novel compound that can specifically block the interaction of this metastasis-inducing protein S100A4 with its target inside the cell. Researchers in the Department of Chemistry then synthesised a simpler chemical and connected it to a warhead which stimulates cells’ normal protein-degrading machinery. This compound now works at very low doses to inhibit properties associated with metastasis, an improvement of over 20 000-fold on the original unarmed inhibitor, with virtually no toxic side effects. Moreover, in collaboration with Chinese researchers at Nanjing Medical School, they have shown that this compound inhibits metastasis in similar metastatic tumours in mice, suggesting a potential therapeutic role.

Dr Gemma Nixon, Senior Lecturer in Medicinal Chemistry at the University of Liverpool said: “This is an exciting breakthrough in our research. We now hope to take the next steps, and repeat this study in a large group of animals with similar metastatic cancers so that the efficacy and stability of the compounds can be thoroughly investigated and if necessary improved by further design and syntheses, prior to any clinical trials.”

“Significantly, this particular protein we’re investigating occurs in many different cancers, which could mean this approach may be valid for many other commonly occurring human cancers.”

Source: University of Liverpool

Categories : PaediatricsTags : Leave a comment

How Mother and Infant Sleep Cycles Interact

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Photo by William Fortunato on Pexels

New mothers can expect sleep deprivation in the first few years of baby’s life. But too little sleep can take a toll on the health of both mother and child. Published in Journal of Developmental & Behavioral Pediatrics, a new study from at maternal and infant sleep patterns, identifying predictors and providing recommendations for instilling healthy habits, such as earlier bedtimes and instilling routines.

“The first two years is a really critical period where a lot of development is going on, and sleep is important for health. We wanted to look at the association of mother and infant sleep and whether it changes over time,” said Tianying Cai, now a postdoctoral researcher at Northwestern University.

“We identified two distinct groups, a low maternal sleep group where the mothers get 5 to 6 hours of sleep per night, and an average maternal sleep group, which meets the national recommended sleep guidelines with 7 to 8 hours per night. Children in the low maternal sleep group also slept less, although the difference wasn’t as large as for the mothers,” Cai stated.

Researchers from the University of Illinois Urbana-Champaign followed parents of 464 infants in the first two years of life. Mothers completed surveys about bedtime routines, their child’s sleep duration, night-time waking, and sleep problems at 3, 12, 18, and 24 months of age.

The families were part of STRONG Kids 2, a program at the U. of I. that promotes nutrition and healthy habits in families with young children. STRONG Kids 2 co-directors Barbara Fiese, professor emerita of HDFS, and Sharon Donovan, professor of food science and human nutrition, also contributed to the study.

Mothers who fit the low maternal sleep profile got an average of 5.74 hours of sleep per night at 3 months and 5.9 hours at 12 to 24 months, while their children got 9.6 and 10.52 hours, respectively. In the average sleep profile, mothers got 7.31 hours at 3 months and 7.28 hours at 12 to 24 months, while child sleep averaged 9.99 hours at 3 months and 11 hours at 12 to 24 months.

The research team also identified factors that influence the amount of sleep a mother gets. Not surprisingly, one of the strongest predictors is infant-signalled night-time waking, which means the infant is more likely to alert the parent at night. This could be either because these infants woke more frequently, or because the mothers were more likely to wake up when infants stirred, Cai noted.

Mothers who had longer employment hours were more likely to be in the low sleep group at 3 months, although that was no longer a factor by 12 months. Furthermore, those who breastfed their infant at 12 months were more likely to be in the average sleep group.

Over time, many families transitioned from the low to the average sleep group as infant sleep patterns consolidated. At 3 months, 60% were in the low maternal sleep group and 40% were in the average group, while at 12 months the numbers were reversed. Most of those who were in the average sleep group at 3 months continued to be so throughout the study period.

The researchers found that an earlier bedtime and consistent routines were associated with better sleep patterns, corroborating a previous study from Fiese and Cai.

“If parents can establish early bedtime routines at three months, it improves sleep duration and reduces sleep problems,” Fiese said. “Parents may feel overwhelmed and don’t realise that they have this in their toolkit. Something as simple as setting a regular bedtime early on and having routines, like reading a story to your child before they go to bed. You may not think they’re understanding, but the rhythm of your voice establishes predictability, and you can expand this bedtime routine over the first few years of life.”

The researchers noted they did not observe any significant differences due to demographic characteristics in the sample.

“Maternal education, income, or ethnicity did not predict sleep group memberships across 3 to 24 months; all parents were facing similar challenges. I think having a baby is a great equaliser for a lot of things, although moms who have to go back to work or work longer hours may have more pressures,” Donovan said.

Even so, there are steps everyone can take to improve bedtime habits and sleep patterns.

“Getting kids to bed earlier and trying to meet the American Academy of Pediatrics guidelines is really important because studies have shown that sleep is associated with a lot of neurocognitive outcomes and health in kids. The parents can be quite proactive even early in life to get their kids off on the right foot,” she concluded.

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

Categories : Lab Tests and Imaging Skeletal SystemTags : Leave a comment

A Quick and Inexpensive Test for Osteoporosis

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Photo by Mehmet Turgut Kirkgoz on Unsplash

In osteoporosis, treatment would be most effective with early detection – something not yet possible with current X-ray based osteoporosis diagnostic tests, which lack the requisite sensitivity. Now, researchers reporting in ACS Central Science have developed a biosensor that could someday help identify those most at risk for osteoporosis using less than a drop of blood.

Early intervention is critical to reducing the morbidity and mortality associated with osteoporosis. The most common technique used to measure changes in bone mineral density (BMD) – dual-energy X-ray absorptiometry – is not sensitive enough to detect BMD loss until a significant amount of damage has already occurred. Several genomic studies, however, have reported genetic variations known as single nucleotide polymorphisms (SNPs) that are associated with increased risk for osteoporosis. Using this information, Ciara K. O’Sullivan and colleagues wanted to develop a portable electrochemical device that would allow them to quickly detect five of these SNPs in finger-prick blood samples in a step toward early diagnosis.

The device involves an electrode array to which DNA fragments for each SNP are attached. When lysed whole blood is applied to the array, any DNA matching the SNPs binds the sequences and is amplified with recombinase polymerase that incorporates ferrocene, a label that facilitates electrochemical detection. Using this platform, the researchers detected osteoporosis-associated SNPs in 15 human blood samples, confirming their results with other methods.

As the DNA does not have to be purified from the blood, the analysis can be performed quickly (about 15 minutes) and inexpensively (< $0.5 per SNP). Furthermore, because the equipment and reagents are readily accessible and portable, the researchers say that the device offers great potential for use at point-of-care settings, rather than being limited to a centralised laboratory. The technology is also versatile and can be readily adapted to detect other SNPs, as the researchers showed previously when identifying drug resistance in Tuberculosis mycobacterium from sputum and cardiomyopathy risk from blood. Although the device does not diagnose osteoporosis itself, it might help physicians identify people whom they should monitor more closely.

Source: Chemical Society