Day: April 5, 2024

Categories : Cancer GastrointestinalTags :

Bacteria Subtype Linked to Growth in up to 50% of Human Colorectal Cancers

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Human colon cancer cells. Credit: National Cancer Institute

Researchers at Fred Hutchinson Cancer Center have found that a specific subtype of a microbe commonly found in the mouth is able to travel to the gut and grow within colorectal cancer tumours. This microbe is also a culprit for driving cancer progression and leads to poorer patient outcomes after cancer treatment.

The findings, published in Nature, could help improve therapeutic approaches and early screening methods for colorectal cancer, which is the second most common cause of cancer deaths in adults in the U.S. according to the American Cancer Society.

Examining colorectal cancer tumours removed from 200 patients, the Fred Hutch team measured levels of Fusobacterium nucleatum, a bacterium known to infect tumours. In about 50% of the cases, they found that only a specific subtype of the bacterium was elevated in the tumour tissue compared to healthy tissue.

The researchers also found this microbe in higher numbers within stool samples of colorectal cancer patients compared with stool samples from healthy people.

“We’ve consistently seen that patients with colorectal tumours containing Fusobacterium nucleatum have poor survival and poorer prognosis compared with patients without the microbe,” explained Susan Bullman, PhD, Fred Hutch cancer microbiome researcher and co-corresponding study author. “Now we’re finding that a specific subtype of this microbe is responsible for tumour growth. It suggests therapeutics and screening that target this subgroup within the microbiota would help people who are at a higher risk for more aggressive colorectal cancer.”

In the study, Bullman and co-corresponding author Christopher D. Johnston, PhD, Fred Hutch molecular microbiologist, along with the study’s first author Martha Zepeda-Rivera, PhD, a Washington Research Foundation Fellow and Staff Scientist in the Johnston Lab, wanted to discover how the microbe moves from its typical environment of the mouth to a distant site in the lower gut and how it contributes to cancer growth.

First they found a surprise that could be important for future treatments. The predominant group of Fusobacterium nucleatum in colorectal cancer tumours, thought to be a single subspecies, is actually composed of two distinct lineages known as “clades.”

“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” Johnston explained. “We have bacterial strains that are so phylogenetically close that we thought of them as the same thing, but now we see an enormous difference between their relative abundance in tumours versus the oral cavity.”

By separating out the genetic differences between these clades, the researchers found that the tumour-infiltrating Fna C2 type had acquired distinct genetic traits suggesting it could travel from the mouth through the stomach, withstand stomach acid and then grow in the lower gastrointestinal tract. The analysis revealed 195 genetic differences between the clades.

Then, comparing tumour tissue with healthy tissue from patients with colorectal cancer, the researchers found that only the subtype Fna C2 is significantly enriched in colorectal tumour tissue and is responsible for colorectal cancer growth.

Further molecular analyses of two patient cohorts, including over 200 colorectal tumours, revealed the presence of this Fna C2 lineage in approximately 50% of cases.

The researchers also found in hundreds of stool samples from people with and without colorectal cancer that Fna C2 levels were consistently higher in colorectal cancer.

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston said.

Source: Fred Hutchinson Cancer Center

Categories : Ageing Medical Research & TechnologyTags :

Introducing Tardigrade Proteins into Human Cells can Slow Metabolism

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Scanning electron micrograph of an adult tardigrade. Source: Wikimedia Commons

University of Wyoming researchers have gained further insight into how tardigrades survive extreme conditions and shown that proteins from the microscopic creatures expressed in human cells can slow down molecular processes.

This makes the tardigrade proteins potential candidates in technologies centred on slowing the aging process and in long-term storage of human cells.

The new study, published in the journal Protein Science, examines the mechanisms used by tardigrades to enter and exit from suspended animation when faced by environmental stress.

Led by Senior Research Scientist Silvia Sanchez-Martinez in the lab of UW Department of Molecular Biology Assistant Professor Thomas Boothby, the research provides additional evidence that tardigrade proteins eventually could be used to make life-saving treatments available to people where refrigeration is not possible — and enhance storage of cell-based therapies, such as stem cells.

Measuring less than half a millimetre long, tardigrades can survive being completely dried out; being frozen to just above absolute zero; heated to more than 150°C; survive radiation of several thousand times a human’s lethal dose; and even survive the vacuum of outer space.

They survive by entering a state of suspended animation called biostasis, using proteins that form gels inside of cells and slow down life processes, according to the new UW-led research.

Co-authors of the study are from institutions including the University of Bristol in the United Kingdom, Washington University in St. Louis, the University of California-Merced, the University of Bologna in Italy and the University of Amsterdam in the Netherlands.

Sanchez-Martinez, who came from the Howard Hughes Medical Institute to join Boothby’s UW lab, was the lead author of the paper.

“Amazingly, when we introduce these proteins into human cells, they gel and slow down metabolism, just like in tardigrades,” Sanchez-Martinez says.

“Furthermore, just like tardigrades, when you put human cells that have these proteins into biostasis, they become more resistant to stresses, conferring some of the tardigrades’ abilities to the human cells.”

Importantly, the research shows that the whole process is reversible: “When the stress is relieved, the tardigrade gels dissolve, and the human cells return to their normal metabolism,” Boothby says.

“Our findings provide an avenue for pursuing technologies centred on the induction of biostasis in cells and even whole organisms to slow aging and enhance storage and stability,” the researchers concluded.

Previous research by Boothby’s team showed that natural and engineered versions of tardigrade proteins can be used to stabilize an important pharmaceutical used to treat people with hemophilia and other conditions without the need for refrigeration.

Tardigrades’ ability to survive being dried out has puzzled scientists, as the creatures do so in a manner that appears to differ from a number of other organisms with the ability to enter suspended animation.

Source: University of Wyoming

Categories : Environmental Effects Neurodegenerative DiseasesTags :

Risk Factors for Faster Aging in the Brain Revealed in New Study

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Source: CC0

Researchers from the Nuffield Department of Clinical Neurosciences at the University of Oxford have used data from UK Biobank participants to reveal that diabetes, traffic-related air pollution and alcohol intake are the most harmful out of 15 modifiable risk factors for dementia.

The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age.

They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer’s disease.

In this new study, published in Nature Communications, they investigated the genetic and modifiable influences on these fragile brain regions by looking at the brain scans of 40 000 UK Biobank participants aged over 45.

The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age.

They classified these modifiable risk factors into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialisation, diet, physical activity, and education.

Prof Gwenaëlle Douaud, who led this study, said: “We know that a constellation of brain regions degenerates earlier in aging, and in this new study we have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution – increasingly a major player in dementia – and alcohol, of all the common risk factors for dementia.”

“We have found that several variations in the genome influence this brain network, and they are implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s diseases, as well as with the two antigens of a little-known blood group, the elusive XG antigen system, which was an entirely new and unexpected finding.”

Prof Lloyd Elliott, a co-author from Simon Fraser University in Canada, concurs: ‘In fact, two of our seven genetic findings are located in this particular region containing the genes of the XG blood group, and that region is highly atypical because it is shared by both X and Y sex chromosomes.

This is really quite intriguing as we do not know much about these parts of the genome; our work shows there is benefit in exploring further this genetic terra incognita.’

Importantly, as Prof Anderson Winkler, a co-author from the National Institutes of Health and The University of Texas Rio Grande Valley in the US, points out: “What makes this study special is that we examined the unique contribution of each modifiable risk factor by looking at all of them together to assess the resulting degeneration of this particular brain ‘weak spot’. It is with this kind of comprehensive, holistic approach – and once we had taken into account the effects of age and sex – that three emerged as the most harmful: diabetes, air pollution, and alcohol.”

This research sheds light on some of the most critical risk factors for dementia, and provides novel information that can contribute to prevention and future strategies for targeted intervention.

Source: University of Oxford

Categories : Expert Opinion IT in HealthcareTags :

The Digital Nurse: Redefining the Future of Healthcare in South Africa

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Sandra Sampson, Director at Allmed

By Sandra Sampson, Director at Allmed

The South African healthcare landscape is undergoing a transformative shift, driven by the rapid advancement of technology. At the forefront of this change is the rise of the “digital nurse,” a testament to the increasing integration of technology into the nursing profession. This transformation is not only streamlining processes; it is addressing critical challenges like the nation’s nurse shortage while ultimately improving patient care.

Embracing convenience and accessibility

Virtual platforms have become commonplace in the nursing world, facilitating efficient and accessible professional development for nurses through online meetings, networking opportunities, and educational resources. This fosters a more connected and knowledgeable nursing community, better equipped to serve patients.

Telehealth consultations, another facet of digital nursing currently revolutionising patient care, provide convenient and accessible medical consultations from the comfort of one’s home, eliminating long wait times and unnecessary travel.

Mitigating nurse shortages and ensuring quality care

South Africa grapples with a significant nurse shortage, placing a strain on the healthcare system to which digital nursing offers a practical potential solution. By leveraging technology, nurses can effectively manage larger patient volumes, reducing the burden on the existing workforce and optimising resource allocation. Remote monitoring systems and AI-powered tools further empower nurses by providing real-time patient data and facilitating early intervention, ultimately improving the quality of care delivered.

Additionally, embracing technology ensures that patients, even in underserved areas, receive quality care. The efficiency gained through virtual platforms allows nurses to allocate their time effectively, addressing minor health concerns remotely and reducing the strain on healthcare facilities for non-emergency cases.

However, it must be pointed out that although leveraging technology allows nurses to effectively manage larger patient volumes, which can alleviate the strain on the current system, this doesn’t necessarily mean fewer nurses are needed, but rather that technology empowers existing numbers to reach a wider patient base to deliver more efficient, personalised care.

Evolving alongside technology: the digital nurse of tomorrow

As the healthcare industry embraces digital technologies, the role of the nurse will continue to expand. While traditional nursing skills will remain essential, the “digital nurse” of the future must possess additional competencies.  Acquiring proficiency in digital tools and equipment, along with the capability to interpret and analyse digital data, will be crucial for delivering effective patient care. However, the most critical attribute for the digital nurse will be the willingness to adapt and embrace constant technological advancements. This will require a mindset shift that comes with acknowledging that traditional methods might not be sufficient in the face of evolving patient needs.

The challenges and opportunities in change

While the adoption of digital nursing brings numerous benefits, challenges remain. Resistance from individuals accustomed to traditional healthcare practices is one hurdle. However, with the younger generation being more adaptable, the shift towards digital nursing is expected to gain wider acceptance as technology advances. To ensure the success of this digital-first healthcare, it will be necessary to focus our attention on upskilling, which means recognising that continuous training and development programs are vital for nurses to remain proficient in the face of change.

On the flip side, a change in perspective from nursing professionals themselves will be necessary. This means embracing a growth mindset and being open towards new technologies to adapt and thrive in the digital age. Lastly, healthcare professionals as a whole need to bear in mind that transformation is essential to meet the evolving needs of patients, which includes catering to a growing preference for digital healthcare solutions. Continuing to meet the needs of patients is the only guaranteed way for nursing professionals to ensure their relevance in the future. By embracing technology and fostering a culture of continuous learning, South Africa can empower its nurses to become the digital healthcare leaders of tomorrow.

Categories : Cardiovascular Disease GastrointestinalTags :

Certain Gut Bacteria Linked to Reduced Cardiovascular Disease Risk

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers has found that microbes in the gut may affect cardiovascular disease as well. In a study published in Cell, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.

Researchers at the Broad Institute of MIT and Harvard along with Massachusetts General Hospital analysed metabolites and microbial genomes from more than 1400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease.

The team discovered that bacteria called Oscillibacter take up and metabolise cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member and a professor at Harvard Medical School and Massachusetts General Hospital.

Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.

Cholesterol cues

In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person’s triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.

In the new study, the Broad team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the Framingham Heart Study.

“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”

More than 16 000 associations between microbes and metabolic traits were found, one of them particularly strong: People with several species of bacteria from the Oscillibacter genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the Oscillibacter genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria.

The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included Oscillibacter.

After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain Oscillibacter in the lab.

The team found another gut bacterial species, Eubacterium coprostanoligenes, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had previously shown is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with Oscillibacter on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.

Microbial messages

The human gut microbiome remains mostly unmapped, but the team believes they have paved the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.

“There are many clinical studies trying to do faecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”

“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”

Source: Broad Institute of MIT and Harvard