Comment

Comment by Dr. Krishna Kumari Challa on December 6, 2024 at 11:16am

Scientists have data representing genetic material from 50,000 E. coli samples gathered from four continents. When they studied these, they saw that the ability to produce the toxin is very limited and is primarily found in two particular genotypes of E. coli bacteria. Both of these circulate frequently in Norway and they are also the main genotypes causing infections in the bloodstream in the country.
In contrast, these genotypes of bacteria are rarely found in countries of South Asia.
The scientists involved in this study have therefore put forward a number of hypotheses on which ecological conditions drive these unwanted bacterial families away from certain population groups.
If scientists can succeed in developing vaccines against the harmful type of E. coli that produces colibactin, or a form of probiotics, this would result in notable public health benefits. These measures could eliminate the unwanted colibactin-producing bacteria from the intestines.

Tommi Mäklin et al, Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli, The Lancet Microbe (2024). DOI: 10.1016/j.lanmic.2024.101015. www.sciencedirect.com/science/ … ii/S2666524724002830

Part 2

Comment by Dr. Krishna Kumari Challa on December 6, 2024 at 11:09am

Scientists explore role of intestinal bacteria in cancer prevention

The link between intestinal bacteria and cancer

Certain intestinal bacteria are found more frequently in some countries such as Norway than in a number of other countries and there is also a higher incidence of bladder cancer, bowel cancer and prostate cancer. These findings may lead to new opportunities for preventing these types of cancer, according to a new study.

Previous studies have shown that a toxin produced by certain bacteria in order to dominate inside the intestine, causes damage to healthy cells and increases the risk of developing bowel cancer.

In a new study, scientists examined the incidence of bladder, colon, rectal and prostate cancer and compared this to the prevalence of two toxin-producing E. coli bacteria in the countries concerned. E. coli is the most common cause of urinary tract infections and bacterial infections in the bloodstream worldwide. Norway has a higher incidence of bladder cancer and colorectal cancer compared with many other countries.

In the course of the study, scientists also found that the prevalence of these two E. coli bacteria was higher in Norway. When they compared equivalent data from several different countries, they discovered a clear pattern: the fewer of these E. coli bacteria that circulate in the population, the lower the incidence of these types of cancer, and vice versa, and the study recently published in The Lancet Microbe confirms this.

In recent years, intense research has been carried out internationally on the link between the toxin produced by these bacteria, called colibactin, and several types of cancer. The research was initiated after groundbreaking studies revealed that colibactin damages DNA in intestinal cells and scientists produced models of intestinal organs and saw that the toxin-producing E. coli resulted in cancer in the models.

Part 1

Comment by Dr. Krishna Kumari Challa on December 6, 2024 at 10:37am

How hummingbirds fly and feed

Comment by Dr. Krishna Kumari Challa on December 6, 2024 at 9:42am

Engineered immune cells to tame inflammation

When the immune system overreacts and starts attacking the body, the only option may be to shut the entire system down and risk developing infections or cancer. But now, scientists  may have found a more precise way to dial the immune system down.

The technology uses engineered T cells that act as immune "referees" to soothe overreacting immune responses. They also can mop up inflammatory molecules.

The new approach could be used to stop the body from rejecting transplanted organs and tissues, such as pancreatic islet cells, which are sometimes used to treat type 1 diabetes. That way, recipients would not need to take harsh immunosuppressant drugs.

This technology can put the immune system back into balance.

The research The team adapted the suppressor cells' anti-inflammatory abilities to work in CD4 immune cells. These are the same cells that are used to make cancer-killing CAR T cells. They also gave these cells a molecular sensor to guide them to their target tissue in the body.

Proof of principle in type 1 diabetes :

The scientists tailored a batch of immune referees to search for human pancreatic islet cells and then produce TGF-Beta and CD25, molecules that can muzzle killer T cells.

They introduced the engineered referee cells into mice that had received a transplant of human islet cells, modeling the treatment for type 1 diabetes.

The referee cells found the vulnerable islet cells and stopped the killer T cells from attacking, and the islet cells survived.

 Nishith R. Reddy et al, Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs, Science (2024). DOI: 10.1126/science.adl4793. www.science.org/doi/10.1126/science.adl4793

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 2:19pm

To get the cell to use homology-directed repair, the researchers recently began using a molecule called AZD7648, which blocks fast repair and forces the cell to use homology-directed repair. This approach is expected to accelerate the development of more efficient gene therapies. Initial studies with these new therapies have been good. Too good to be true, as it turned out.

A research group led by Corn has discovered that the use of AZD7648 has serious side effects. The study has been published in the journal Nature Biotechnology.

Although AZD7648 promotes precise repair and thus precise gene editing using the CRISPR-Cas9 system as hoped, in a significant proportion of cells this has led to massive genetic changes in a part of the genome that was expected to be modified without scarring.

The ETH researchers found that these changes resulted in the simple deletion of thousands and thousands of DNA building blocks, known as bases. Even whole chromosome arms broke off. This makes the genome unstable, with unpredictable consequences for the cells edited by the technique.

When the researchers analyzed the genome at the sites where it had been edited, it looked correct and precise. But when they analyzed the genome more broadly, they saw massive genetic changes. These are not seen when you only analyze the short, edited section and its immediate neighborhood.

The extent of the negative effects surprised the researchers. In fact, they suspect that they do not yet have a complete picture of the full extent of the damage because they did not look at the entire genome when analyzing the modified cells, only partial regions.

New tests, approaches and regulations are therefore needed to clarify the extent and potential of the damage.

The development of any new technology is a rocky road. One stumble does not mean we give up on the technology, say the researchers.

Gene therapies based on the CRISPR-Cas system have already been successfully used in clinical practice. In recent years, for example, a hundred patients suffering from the hereditary disease sickle cell anemia have been treated with CRISPR-Cas-based therapeutics—without AZD7648.

"All patients are considered cured and have no side effects".

Grégoire Cullot et al, Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02488-6

Part 2

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 2:15pm

Serious side effect of using CRISPR-Cas gene scissors uncovered: AZD7648 molecule can destroy parts of genome

Genome editing with various CRISPR-Cas molecule complexes has progressed rapidly in recent years. Hundreds of labs around the world are now working to put these tools to clinical use and are continuously advancing them.

CRISPR-Cas tools allow researchers to modify individual building blocks of genetic material in a precise and targeted manner. Gene therapies based on such gene editing are already being used to treat inherited diseases, fight cancer and create drought- and heat-tolerant crops.

The CRISPR-Cas9 molecular complex, also known as genetic scissors, is the most widely used tool by scientists around the world. It cuts the double-stranded DNA at the exact site where the genetic material needs to be modified. This contrasts with newer gene-editing methods, which do not cut the double strand.

The cut activates two natural repair mechanisms that the cell uses to repair such damage: a fast but imprecise one that reconnects only the ends of the cut DNA, and a slow and precise one that is not activated in every case. The latter requires a copyable template for repair to accurately rejoin the DNA at the cut site.

The slow variant is called homology-directed repair. Researchers want to use this method of repair because it allows the precise integration of individual DNA segments into a desired gene region. The approach is very flexible and can be used to repair different disease genes.

In principle, it could be used to cure any disease.

Part 1

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 11:29am

Interestingly, the cancer cells themselves were unable to use fructose readily as a nutrient because they do not express the right biochemical machinery. Liver cells do. This allows them to convert fructose into LPCs, which they can secrete to feed tumors.

Gary Patti, Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer, Nature (2024). DOI: 10.1038/s41586-024-08258-3. www.nature.com/articles/s41586-024-08258-3

Part 2

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 11:27am

Research reveals how fructose in diet enhances tumor growth

Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener in beverages and ultra-processed foods.

New research  shows that dietary fructose promotes tumor growth in animal models of melanoma, breast cancer and cervical cancer. However, fructose does not directly fuel tumors, according to the study published Dec. 4 in the journal Nature.

Scientists discovered that the liver converts fructose into usable nutrients for cancer cells, a compelling finding that could open up new avenues for care and treatment of many different types of cancer.

Using metabolomics—a method of profiling small molecules as they move through cells and across different tissues in the body—the researchers concluded that one way in which high levels of fructose consumption promote tumor growth is by increasing the availability of circulating lipids in the blood. These lipids are building blocks for the cell membrane, and cancer cells need them to grow.

Researchers looked at numerous different cancers in various tissues throughout the body, and they all followed the same mechanism.

Scientists have long recognized that cancer cells have a strong affinity for glucose, a simple sugar that is the body's preferred carbohydrate-based energy source.

In terms of its chemical structure, fructose is similar to glucose. They are both common types of sugar, with the same chemical formula, but they differ in how the body metabolizes them. Glucose is processed throughout the whole body, while fructose is almost entirely metabolized by the small intestine and liver.

Both sugars are found naturally in fruits, vegetables, dairy products and grains. They are also added as sweeteners in many processed foods. 

 The researchers found that added fructose promoted tumor growth without changing body weight, fasting glucose or fasting insulin levels. It had a rather dramatic impact. In some cases, the growth rate of the tumors accelerated by two-fold or even higher.

The researchers attempted to repeat a version of this test by feeding fructose to cancer cells isolated in a dish, the cells did not respond. In most cases they grew almost as slowly as if we gave them no sugar at all.

Part 1

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 11:40am

Toxin in blood of kidney disease patients could contribute to stroke risk, study suggests

Scientists have revealed that a toxin found in the blood of patients with chronic kidney disease (CKD) damages the body's protective blood–brain barrier, likely contributing to the risk of stroke.

Researchers investigated the effect on the central nervous system of "p-cresol sulfate," a molecule produced by the gut microbiome. 

While this molecule is efficiently cleared by the kidneys in healthy people, it accumulates in the blood of patients with CKD.
Investigating the effect of p-cresol sulfate on human tissue and in mice—and replicating their results using blood samples from dialysis patients—the team found that the toxin triggers a process which activates two enzymes that damage the wall of brain blood vessels.

The researchers observed how this impairs the critically protective blood–brain barrier, which acts as a shield to prevent harmful substances and toxins in the body from reaching the brain.

Damage to the blood–brain barrier is known to contribute to the risk of stroke, which can be up to 30 times greater in CKD patients than in the general population.

As part of the study, however, the researchers also found that a class of 'inhibitor' type drugs—which can block chemical reactions in the body—showed promising results in being able to prevent this damage from occurring.

In further tests, the team found that a class of enzyme inhibitor drugs was able to block the damaging effects of blood from CKD patients on cells in vitro.

As well as enhanced stroke risk, patients with CKD, including those not yet requiring dialysis, exhibit significant cognitive decline, a change that seems to be at least partly driven by damage to the brain's blood vessels.

 Sita N. Shah et al, Cerebrovascular damage caused by the gut microbe/host co-metabolite p -cresol sulfate is prevented by blockade of the EGF receptor, Gut Microbes (2024). DOI: 10.1080/19490976.2024.2431651

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 10:39am

Seeing through the mystery of an X-ray emissions mechanism

Scientists who study X-rays, lightning and similar phenomena have observed something curious: In lab experiments replicating these occurrences, electrons accelerated between two electrodes can be of a higher energy than the voltage applied.

This defies an assumption in physics that the energy of the electrons should correspond with the voltage applied.

Recently, a team of  researchers used mathematical modeling to explain the underlying mechanism at play. They published their results in Physical Review Letters.

Through mathematical modeling, they  demonstrated that an energy feedback process is responsible for this occurrence.

According to them when the electrons interact with the material of the electrode, they emit X-rays, which are made of photons—massless, charge-less particles that comprise light. Some of these photons propagate backward, enabling more electrons to release from the other electrode.

A small group of these electrons have energy corresponding to the original energy. Then they accelerate again, and the process continues through several cycles. The researchers modeled this very high energy process.

Their model also helped explain why electrodes of different shapes and materials produced this effect to varying degrees. We get maximum effect when we have flat electrodes, and a minimized effect when the electrodes are needle-like. 

This makes sense, because the large surface areas of the flat electrodes are good for the interaction between the electrons and photons and the way they bounce back and forth. When the surface area is reduced, the effect is minimized.

The researchers also examined via simulation and modeling how the phenomenon emerges with different materials.

Tungsten is the standard material used for X-ray production, and we know it's a good material for this. It is a robust material for electron production used in current in X-ray machines.

The researchers said that their findings may be useful for the development of new ways of producing X-rays in the future. Specifically, they said that the work may stimulate new research on the production of energetic electrons from solid materials, potentially making X-rays machines faster and more light weight and compact.

Victor P. Pasko et al, Photoelectric Feedback Mechanism for Acceleration of Runaway Electrons in Gas Discharges at High Overvoltages, Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.235301

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