Comment

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:36pm

To test the particles, the researchers first injected them into the stomachs of mice, without using the delivery capsule. The RNA that they delivered codes for a reporter protein that can be detected in tissue if cells successfully take up the RNA. The researchers found the reporter protein in the stomachs of the mice and also in the liver, suggesting that RNA had been taken up in other organs of the body and then carried to the liver, which filters the blood.

Next, the researchers freeze-dried the RNA-nanoparticle complexes and packaged them into their drug delivery capsules. Working with scientists at Novo Nordisk, they were able to load about 50 micrograms of mRNA per capsule, and delivered three capsules into the stomachs of pigs, for a total of 150 micrograms of mRNA. This is the more than the amount of mRNA in the COVID vaccines now in use, which have 30 to 100 micrograms of mRNA.

In the pig studies, the researchers found that the reporter protein was successfully produced by cells of the stomach, but they did not see it elsewhere in the body. In future work, they hope to increase RNA uptake in other organs by changing the composition of the nanoparticles or giving larger doses. However, it may also be possible to generate a strong immune response with delivery only to the stomach.

"There are many immune cells in the gastrointestinal tract, and stimulating the immune system of the gastrointestinal tract is a known way of creating an immune response.

 Giovanni Traverso, Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections, Matter (2022). DOI: 10.1016/j.matt.2021.12.022. www.cell.com/matter/fulltext/S2590-2385(21)00680-9

https://medicalxpress.com/news/2022-01-pill-rna-stomach-vaccines.ht...

Part 3

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Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:35pm

For several years, scientists have been developing novel ways to deliver drugs to the gastrointestinal tract. In 2019, the researchers designed a capsule that, after being swallowed, can place solid drugs, such as insulin, into the lining of the stomach.

The pill, about the size of a blueberry, has a high, steep dome inspired by the leopard tortoise. Just as the tortoise is able to right itself if it rolls onto its back, the capsule is able to orient itself so that its contents can be injected into the lining of the stomach.

In 2021, the researchers showed that they could use the capsule to deliver large molecules such as monoclonal antibodies in liquid form. Next, the researchers decided to try to use the capsule to deliver nucleic acids, which are also large molecules.

Nucleic acids are susceptible to degradation when they enter the body, so they need to be carried by protective particles. For this study, the  team used a new type of polymeric nanoparticle  they had recently developed.

These particles, which can deliver RNA with high efficiency, are made from a type of polymer called poly(beta-amino esters). The MIT team's previous work showed that branched versions of these polymers are more effective than linear polymers at protecting nucleic acids and getting them into cells. They also showed that using two of these polymers together is more effective than just one.

Part 2

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:33pm

A pill that releases RNA in the stomach could offer a new way to administer vaccines

Like most vaccines, RNA vaccines have to be injected, which can be an obstacle for people who fear needles. Now, a team of  researchers has developed a way to deliver RNA in a capsule that can be swallowed, which they hope could help make people more receptive to them.

In addition to making vaccines easier to tolerate, this approach could also be used to deliver other kinds of therapeutic RNA or DNA directly to the digestive tract, which could make it easier to treat gastrointestinal disorders such as ulcers.

Nucleic acids, in particular RNA, can be extremely sensitive to degradation particularly in the digestive tract. Overcoming this challenge opens up multiple approaches to therapy, including potential vaccination through the oral route.

In a new study, researchers showed that they could use the capsule they developed to deliver up to 150 micrograms of RNA—more than the amount used in mRNA COVID vaccines—in the stomach of pigs.

part 1

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:55am

Melting causes gradients in the temperature of the water near the ice, which causes the liquid at different places to have different densities. This generates flows due to gravity—with heavier liquid sinking and lighter fluid rising—and such flows along the surface lead to different rates of melting at different locations and thus changes in shape.

The strange bit of physics is that liquid water has a highly unusual dependence of density on temperature, in particular a maximum of density at about 4 degrees C. "This 'density anomaly' makes water unique in comparison to other fluids."

The research shows that this property is responsible for producing very different flows, depending on the precise value of the water temperature. The downward pinnacles at low temperatures are associated with upward flows, while the upward pinnacles have downward flows. The scalloped patterns form because upward flows very near the surface interact with downward flows further away, destabilizing into vortices that carve pits into the ice.

Scott Weady et al, Anomalous Convective Flows Carve Pinnacles and Scallops in Melting Ice, Physical Review Letters (2022). DOI: 10.1103/PhysRevLett.128.044502

https://phys.org/news/2022-01-scientists-uncover-ice-temperature.ht...

Part 2

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:53am

Scientists uncover how the shape of melting ice depends on water temperature

A team of mathematicians and physicists has discovered how ice formations are shaped by external forces, such as water temperature. Its newly published research may offer another means for gauging factors that cause ice to melt.

The shapes and patterning of ice are sensitive indicators of the environmental conditions at which it melted, allowing researchers to 'read' the shape to infer factors such as the ambient water temperature. This  helps to understand how melting induces unusual flow patterns that in turn affect melting, which is one of the many complexities affecting the ice on our planet.

The researchers studied, through a series of experiments, the melting of ice in water and, in particular, how the water temperature affects the eventual shapes and patterning of ice. To do so, they created ultra-pure ice, which is free of bubbles and other impurities. The team recorded the melting of ice submerged into water tanks in a "cold room," which is similar to a walk-in refrigerator whose temperature is controlled and varied.

They focused on the cold temperatures—0 to 10 degrees Celsius—at which ice in natural waters typically melts, and  found a surprising variety of shapes that formed. 

Specifically, at very cold temperatures—those under about 5 degrees C—the pieces take on the shape of a spike or "pinnacle" pointing downward—similar to an icicle, but perfectly smooth (with no ripples). For temperatures above approximately 7 degrees C, the same basic shape forms, but upside down—a spike pointing upward. For in between temperatures, the ice has wavy and rippled patterns melted into its surface. Similar patterns, called "scallops," are found on icebergs and other ice surfaces in nature.

These shape differences are due to changes in water flows, which are determined by their temperatures.

Part 1

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:49am

Reference substances play an essential role in the interpretation of a screen, so they should be carefully evaluated and tested. The compounds identified by the cell painting show a wide variety of chemical scaffolds and even small chemical modifications can have a dramatic impact on the tubulin-binding properties of a compound. This risk is ubiquitous, especially during the compound optimization phase, where existing atoms are exchanged or removed and new atoms are added in order to improve the pharmacological properties. Additional morphological profiling during the search for hits and their optimization could not only help unmask side effects such as tubulin modulation early on, but also identify desired and new bioactivities. Moreover, this approach could save time and money as it helps to early assess whether a promising substance has what it takes to become a useful compound or not.

Mohammad Akbarzadeh, Ilka Deipenwisch, Beate Schoelermann, Axel Pahl, Sonja Sievers, Slava Ziegler, Herbert Waldmann. Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds. Cell Chemical Biology, 2021; DOI: 10.1016/j.chembiol.2021.12.009

https://researchnews.cc/news/11353/Morphological-fingerprinting-cou...

Part 2

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:48am

Morphological fingerprinting could help identify side effects and new bioactive compounds in drug discovery

Pharmaceutical researchers speak of a hit when they come across a promising substance with a desired effect in early drug discovery. Unfortunately, hits are rarely bull's-eyes, often showing undesirable side effects that not only complicate the search for new hits, but also the subsequent development into a drug. A new study  could now help to better identify one of the most frequently observed side effects already in early drug discovery, but also to find new bioactivities.

The most commonly used cancer drugs contain active substances that manipulate the cell's cytoskeleton by binding to microtubules. This can disrupt cell division as well as impair other essential processes, and leads to cell death. Such an effect is of course not desirable for other therapies. However, microtubules' surface has many deep binding pockets that makes them particularly susceptible to modulation by a wide variety of chemical substances with diverse chemical scaffolds.

In the search for and development of new active substances, the study of known side effects plays a crucial role, especially when one considers that about 13 years and more than one billion US dollars are needed to develop a new drug. Although there are already standardized test procedures (screens) for identifying undesirable side effects, they certainly do not cover all targets in cells, often do not correctly reflect the cellular context, or they allow targets to be overlooked, e.g. binding to tubulin. Thus, drug discovery is always biased to a certain extent.

Researchers now  used a new strategy to reliably detect side effects, such as the disruption of microtubules, at an early stage of the search for bioactive compounds. To do this, the researchers employed the so-called "cell painting" approach. Here, several functional areas of the cell are stained and then examined microscopically for changes after the addition of chemical substances. This enables recording hundreds of cellular parameters in a single morphological fingerprint. If one detects similarity of this fingerprint to those of known reference substances, conclusions about the effect of the unknown substance can be drawn. The value of this approach lies in the possibility of creating fingerprints for thousands of substances in a high-throughput process. This way, the researchers revealed that more than 1% of about 15,000 studied substances had a tubulin-modulating effect. Among them was also a large number of known reference substances for which an influence on tubulin was previously unknown.

Part 1

Comment by Dr. Krishna Kumari Challa on January 31, 2022 at 6:43am

The team used electronic data for patients admitted to Nottingham University Hospitals NHS Trust between February 2020 and September 2021 with Covid-19 infection. Pulse oximetry measurements with a paired blood gas measurement within a half an hour window were compared.

Mean differences between pulse oximetry and blood gas oxygen saturations were recorded by ethnicity of White, Mixed, Asian, and Black patients, and were also split up by level of oxygen saturation as measured by arterial blood gases.

There were differences in oxygen saturations (amounts of oxygen in the blood), between the pulse oximetry arterial blood gas readings in all groups. The highest difference was in the Mixed ethnicity group which was nearly 7% higher in the oximetry reading, with the lowest in the White group at 3.2% higher than the true measurement from arterial blood gases. A reading of 5.4% higher using pulse oximetry was found in the Black group of participants and 5.1% higher in the Asian population.

The difference between the readings also increased in the clinically important range of 85 to 89%, when many clinical decisions are made. Mean values as measured by pulse oximeter were higher than reality in individuals with a recorded Black and Asian ethnicity, compared to those of a White ethnicity.

The findings of the research are important as high levels of skin pigmentation are associated with ethnic groups who have a poorer outcome from Covid-19 infection, and would require the most accurate oxygen measurements available in order to deliver the most appropriate and timely treatment.

1. Colin J Crooks, Joe West, Joanne R Morling, Mark Simmonds, Irene Juurlink, Steve Briggs, Simon Cruickshank, Susan Hammond-Pears, Dominick Shaw, Timothy R Card, Andrew W Fogarty. Pulse oximeters' measurements vary across ethnic groups: An observational study in patients with Covid-19 infection. European Respiratory Journal, 2022; 2103246 DOI: 10.1183/13993003.03246-2021

https://researchnews.cc/news/11340/Pulse-oximeter-measurements-of-b...

Part 2

Comment by Dr. Krishna Kumari Challa on January 31, 2022 at 6:42am

Pulse oximeter measurements of blood oxygen levels are unreliable in assessing severity of Covid-19 pneumonia

The severity of Covid-19 pneumonia can be difficult to assess in people from different ethnic groups, due to inaccurate readings from a device that measures the level of oxygen in the blood of patients.

The findings of the research, published in the European Respiratory Journal, show that pulse oximeters gave false readings of nearly 7% higher in a group of patients of Mixed ethnicity with Covid-19, compared to White patients at just over 3%. There were also falsely high readings in patients with both Black and Asian ethnicity, which could delay patients receiving the best and most timely treatment for the virus.

Pulse oximetry is a non-invasive test that measures the oxygen saturation level of the blood. It can rapidly detect even small changes in oxygen levels. These levels show how efficiently blood is carrying oxygen to the extremities furthest from the heart, including the arms and legs. Medical professionals routinely use them in primary care and critical care settings like emergency rooms or hospitals to monitor the clinical status of their patients.

The light wave transmission that this technology uses is modified by skin pigmentation and may vary by skin colour. A recent study reported different outputs in patients with Black skin compared to patients with White skin, which has the potential to adversely affect patient care. This led to the Food and Drink Administration in the USA releasing an expression of concern about the accuracy of pulse oximeters in 2021, which led to the current study.

Researchers  made use of the electronic datasets that are collected for clinical use in real time, but archived and available to answer important clinical questions and improve both patient care and patient safety in the future. The NUH Covid-19 Patient Safety Database is anonymised to allow lessons to be learned without compromising individual patient confidentiality. The team included clinicians, managers, statisticians, computer analysts, software coders and data warehouse archivists.

The team of experts from Nottingham used data from patients with Covid-19 infection to look at the difference in blood oxygen levels as measured by pulse oximetry and arterial blood gas tests, spilt into different ethnic groups over a wide range of oxygen saturations. Arterial blood gas tests measure the levels of oxygen in the blood from an artery, and represent the gold standard measurement for oxygen levels.

Part1

Comment by Dr. Krishna Kumari Challa on January 28, 2022 at 12:47pm

How do algae survive excess oxygen?

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