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Comment by Dr. Krishna Kumari Challa on May 11, 2023 at 9:27am

New method for delivering an antioxidant directly to mitochondria in the liver, mitigating oxidative stress

Mitochondria are microscopic organelles found within cells, and are by far the largest producer of the molecule adenosine triphosphate (ATP), which provides energy to many processes in living cells. The process by which mitochondria synthesize ATP generates a large amount of reactive oxygen species (ROS), chemical groups that are highly reactive.

In a healthy cell, the ROS are controlled by the mitochondria; however, when this balance is lost, the excess ROS damages the mitochondria and subsequently cells and tissues. This phenomenon, known as oxidative stress, can cause premature aging and disease. The ROS that cause oxidative stress can be controlled by antioxidants.

A research team has developed a system to deliver antioxidants to mitochondria to mitigate the effects of excess ROS. Their findings have been published in Scientific Reports.

They  developed a drug delivery system which they named CoQ₁₀-MITO-Porter. This system consists of the antioxidant molecule Coenzyme Q₁₀ (CoQ₁₀)—which is also required by mitochondria for ATP production—encapsulated by a lipid nanoparticle that would target mitochondria. 

Variations of the formula for the synthesis of CoQ₁₀-MITO-Porter were tested, and their structures were examined with electron microscopy. CoQ₁₀-MITO-Porter was administered to mice models with acetaminophen-induced liver damage. Acetaminophen overdoses cause excess ROS in mitochondria, which in turn damages cells in the liver. CoQ₁₀-MITO-Porter was transported primarily to the liver and measurably reduced the damage caused by ROS. A further discovery was that downsized CoQ₁₀-MITO-Porter particles with more efficient packaging of CoQ₁₀ were more effective at treating liver damage than the original formulation.

Mitsue Hibino et al, A System that Delivers an Antioxidant to Mitochondria for the treatment of Drug-Induced Liver Injury, Scientific Reports (2023). DOI: 10.1038/s41598-023-33893-7. www.nature.com/articles/s41598-023-33893-7

Comment by Dr. Krishna Kumari Challa on May 11, 2023 at 8:53am

Scientists discover microbes in the Alps and Arctic that can digest plastic at low temperatures

Finding, cultivating, and bioengineering organisms that can digest plastic not only aids in the removal of pollution, but is now also big business. Several microorganisms that can do this have already been found, but when their enzymes that make this possible are applied at an industrial scale, they typically only work at temperatures above 30°C.

The heating required means that industrial applications remain costly to date, and aren't carbon-neutral. But there is a possible solution to this problem: finding specialist cold-adapted microbes whose enzymes work at lower temperatures.

Scientists  knew where to look for such microorganisms: at high altitudes in the Alps, or in the polar regions. When they did that, novel microbial taxa obtained from the 'plastisphere' of alpine and arctic soils were able to break down biodegradable plastics at 15°C. Their findings are published in Frontiers in Microbiology.

How did the ability to digest plastic evolve? Since plastics have only been around since the 1950s, the ability to degrade plastic almost certainly wasn't a trait originally targeted by natural selection.

Microbes have been shown to produce a wide variety of polymer-degrading enzymes involved in the break-down of plant cell walls. In particular, plant-pathogenic fungi are often reported to biodegrade polyesters, because of their ability to produce cutinases which target plastic polymers due their resemblance to the plant polymer cutin.

Discovery of plastic-degrading microbial strains isolated from the alpine and Arctic terrestrial plastisphere, Frontiers in Microbiology (2023). DOI: 10.3389/fmicb.2023.1178474 , www.frontiersin.org/articles/1 … cb.2023.1178474/full

Comment by Dr. Krishna Kumari Challa on May 11, 2023 at 8:42am

Breakthrough research could bring stem cell therapy to the masses

Researchers  have made a significant breakthrough in realizing the promise of stem cell therapy: stem cells that do not trigger an immune response from an immunologically incompatible donor.

In the paper "Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques," published in Nature Biotechnology, the researchers detail how they cloaked a line of hypoimmune pluripotent (HIP) stem cells to evade the normal rejection and destruction obstacles to therapeutic use.

In an experimental setting, hypoimmune pluripotent cells did not trigger an immune cell response. They were also impervious to cytotoxicity incited by wild-type stem cells transplanted along with them, successfully evading direct detection and effects from the enrichment of untargeted threats.

The HIP cells survived unrestricted for 16 weeks (the entire test duration) in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas wild-type cells were vigorously rejected.

In a humanized diabetic mouse model, pancreatic differentiated human HIP cells lasted four weeks and showed evidence of improving the condition. The mice were not immunosuppressed and were not a type match for the cell types used.

An additional long-term test of HIP cells found cell islets 40 weeks after implantation in rhesus macaque recipients without immunosuppression, compared to an unedited wild-type version that was destroyed within a week.

Stem cells have the potential to revolutionize medicine as they can be manipulated to differentiate into various cell types, making them a promising source of new cells for transplantation or regenerative medicine. By introducing stem cells to damaged tissue or organs, it may be possible to regenerate healthy tissue and restore proper function. This has implications for developing new therapies for various diseases, including cancer, heart disease, and neurological disorders.

Xiaomeng Hu et al, Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques, Nature Biotechnology (2023). DOI: 10.1038/s41587-023-01784-x

Comment by Dr. Krishna Kumari Challa on May 11, 2023 at 8:12am

Comment by Dr. Krishna Kumari Challa on May 10, 2023 at 11:53am

A New Way to Activate Dormant Cells in The Retina Could Restore Vision

Degenerative retinal disease is a problem for millions of people worldwide, as light-sensitive cells called photoreceptors at the back of the eye die without being replaced. Thanks to new research, a solution to the problem might not be far off.

Scientists  have come up with a way to transform dormant support neurons called Müller glial cells into tissues that work like cone photoreceptors, which are required for color perception and visual acuity. While the process has only been tested on mice cells, it could eventually be developed into a therapy that can restore vision in people.

Part of the reason the Müller glial cells were chosen for investigation is their ability to be reprogrammed in some animals. Unfortunately it's not a trick that these cells can do in humans.

What's interesting is that these Müller cells are known to reactivate and regenerate retina in fish. But in mammals, including humans, they don't normally do so, not after injury or disease. And we don't yet fully understand why.

Key to the study were the genes Ikzf1 and Ikzf4, and the proteins they produced. These proteins are known as temporal identity factors, already known to play important roles in the development of cells into various types.

The Müller glial cells were isolated and cultured before being reprogrammed using a variety of temporal identity factors, including Ikzf1 and Ikzf4. These factors didn't fully transform the glial cells into cone cells, but they did take on some of the necessary characteristics to function like the photoreceptors.

While glial cells help nourish, regulate, and organize other cells in the eye, the researchers say there's enough of a surplus to safely convert a number of the support cells into the photoreceptor-like cells – crucial for seeing light and identifying colors.

It's early days, but the process could eventually be adapted to work in humans, without the need to transplant any new cells. Further down the line, these findings could also be useful in treating diseases in the brain – being able to replace certain neurons that have been damaged by reprogramming other types of cells.

https://www.pnas.org/doi/10.1073/pnas.2122168120

Comment by Dr. Krishna Kumari Challa on May 10, 2023 at 10:02am

In a previous study, the research team identified the bottleneck in the process of delivery of nanoparticles to stem cells. They showed that the nanoparticles got trapped in bubble-like vesicles that prevented them from getting into the stem cell, but it wasn't clear why.

To understand how to overcome the difficulties posed by the stem cell barrier, the team of researchers studied ways to improve the movement of nanoparticles across the cell membranes, which could carry genetic information that would direct the transformation of a stem cell to its new cell type.

Eventually, they found that coating the nanoparticles in a type of polymer helped them to get into the stem cells.

The coated nanoparticles avoided getting trapped in vesicles, unlike the uncoated ones. In fact, they seemed to circumvent the vesicles altogether and enter the cell more directly.

It's not yet clear why the coating works, but the discovery will help to make the delivery of genetic information to stem cells more efficient so that it is easier to control which cells they become.

However, the team recognizes there is a long way to go before this method can be used clinically.

Wanchuan Ding et al, Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells, Nano Letters (2023). DOI: 10.1021/acs.nanolett.2c04834

Part 2

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Comment by Dr. Krishna Kumari Challa on May 10, 2023 at 9:59am

Researchers overcome stem cell delivery barrier, paving the way for regenerative medicine

A recent study published in Nano Letters has introduced a new method for delivering particles into stem cells, which are notoriously difficult to penetrate. The discovery will make it easier to direct and enhance the processes involved in regenerative medicine.

Regenerative medicine takes advantage of the fact that our body's stem cells can change into many other cell types that are vital for the regeneration of tissue and organs, such as heart or nerve cells.

Each type of cell has specialized properties and functions, so harnessing the potential of stem cell development means that regenerative medicine offers some of the most promising treatments for many diseases. To control the type of cell the stem cells change into, scientists need to reprogram the cells' genes by inserting genetic information into the stem cell's nucleus.

However, stem cells have robust protection to stop anything from getting in, similar to our skin, so manipulating the differentiation of stem cells has been problematic.

The researchers have been working to overcome this using rat stem cells and have created a way to bypass the cells' protective barrier.

As we age, the number of stem cells in our body decreases dramatically. So, to harness their potential to regenerate damaged cell tissue and organs, we need to implant them into the body.

But the introduced stem cells usually die within about a week once they are in the body, yet can take around four weeks to differentiate into other cell types.

So scientists  grew stem cells outside the body. Then using a new method, they can insert specific genetic information into the cells using nanoparticles to cause them to change into a particular type of cell.

Once the cells have differentiated into the target cell type, they put them into the area of the body where there is damaged tissue so that they can help to restore it.

Part 1

Comment by Dr. Krishna Kumari Challa on May 10, 2023 at 9:53am

Lifesaving solution dramatically reduces severe bleeding after childbirth

A new solution, known as E-MOTIVE, could provide a major breakthrough in reducing deaths from childbirth-related bleeding, according to a landmark study published recently (May 9) in the New England Journal of Medicine by researchers from the World Health Organization (WHO).

Postpartum hemorrhage (PPH)—defined as the loss of more than 500 mL of blood within 24 hours after birth—is the leading cause of maternal mortality worldwide. It affects an estimated 14 million women each year and results in around 70,000 deaths, mostly in low and middle-income countries, equivalent to one death every six minutes.

Postpartum hemorrhage is scary, not always predictable, but absolutely treatable. Nonetheless, its impacts around the world are tragic.

The study, which involved more than 200,000 women in four countries, found that objectively measuring blood loss using a simple, low-cost collection device called a "drape" and bundling together WHO-recommended treatments—rather than offering them sequentially—resulted in dramatic improvements in outcomes for women. Severe bleeding—when a woman loses more than a liter of blood after birth—was reduced by 60%, and they were less likely to die.

There was also a substantial reduction in the rate of blood transfusions for bleeding, which is of particular importance in low-income countries where blood is a scarce and expensive resource.

This new approach to treating postpartum hemorrhage could radically improve women's chances of surviving childbirth globally, helping them get the treatment they need when they need it.

The recommended E-MOTIVE package includes early and accurate detection of PPH using a blood-collection drape. This is complemented by an immediate treatment bundle where indicated, including uterine massage, medicines to contract the womb and stop the bleeding, intravenous fluid administration, an examination and, when needed, escalation to advanced care. In the trial, the E-MOTIVE intervention was supported with an implementation strategy consisting of specific training, PPH trolleys or carry cases, engagement of local champions, audits and feedback. All components of the E-MOTIVE intervention can be performed by midwives.

Ioannis Gallos et al, Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2303966

Comment by Dr. Krishna Kumari Challa on May 10, 2023 at 9:44am

The model successfully captured kimberlite eruptions in Africa, Brazil, Russia and partly in the United States and Canada. 

Towards the center of the pillars, mantle plumes rise much faster and carry dense material across the mantle, which may explain chemical differences between kimberlites in different continents.

These  models do not explain some of the kimberlites in Canada, which might be related to a different geological process called "plate subduction." We have so far predicted kimberlites back to one billion years ago, which is the current limit of reconstructions of tectonic plate movements.

 Ömer F. Bodur et al, Kimberlite magmatism fed by upwelling above mobile basal mantle structures, Nature Geoscience (2023). DOI: 10.1038/s41561-023-01181-8

Part 3

Comment by Dr. Krishna Kumari Challa on May 10, 2023 at 9:43am

Kimberlite eruptions leave behind a characteristic deep, carrot-shaped "pipe" of kimberlite rock, which often contains diamonds. Hundreds of these eruptions that occurred over the past 200 million years have been discovered around the world. Most of them were found in Canada (178 eruptions), South Africa (158), Angola (71) and Brazil (70).

Between Earth's solid crust and molten core is the mantle, a thick layer of slightly goopy hot rock. For decades, geophysicists have used computers to study how the mantle slowly flows over long periods of time.

In the 1980s, one study showed that kimberlite eruptions might be linked to small thermal plumes in the mantle—feather-like upward jets of hot mantle rising due to their higher buoyancy—beneath slowly moving continents.

It had already been argued, in the 1970s, that these plumes might originate from the boundary between the mantle and the core, at a depth of 2,900km.

Then, in 2010, geologists proposed that kimberlite eruptions could be explained by thermal plumes arising from the edges of two deep, hot blobs anchored under Africa and the Pacific Ocean.

And last year, scientists reported that these anchored blobs are more mobile than they thought.

Geologists assumed that mantle plumes could be responsible for igniting kimberlite eruptions. However, there was still a big question remaining: how was heat being transported from the deep Earth up to the kimberlites?

Researchers used supercomputers  to create three-dimensional geodynamic models of Earth's mantle. Their models account for the movement of continents on the surface and into the mantle over the past one billion years.

They calculated the movements of heat upward from the core and discovered that broad mantle upwellings, or "pillars of heat," connect the very deep Earth to the surface. Their modeling shows these pillars supply heat underneath kimberlites, and they explain most kimberlite eruptions over the past 200 million years.

Part 2

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