Tag Archives: inflammatory diseases

Nanoscale measurements for osteoarthritis biomarker

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There’s a new technique for measuring hyaluronic acid (HA), which appears to be associated with osteoarthritis. A March 12, 2018 news item on ScienceDaily makes the announcement,

For the first time, scientists at Wake Forest Baptist Medical Center have been able to measure a specific molecule indicative of osteoarthritis and a number of other inflammatory diseases using a newly developed technology.

This preclinical [emphasis mine] study used a solid-state nanopore sensor as a tool for the analysis of hyaluronic acid (HA).

I looked at the abstract for the paper (citation and link follow at end of this post) and found that it has been tested on ‘equine models’. Presumably they mean horses or, more accurately, members of the horse family. The next step is likely to be testing on humans, i.e., clinical trials.

A March 12, 2018 Wake Forest Baptist Medical Center news release (also on EurekAlert), which originated the news item, provides more details,

HA is a naturally occurring molecule that is involved in tissue hydration, inflammation and joint lubrication in the body. The abundance and size distribution of HA in biological fluids is recognized as an indicator of inflammation, leading to osteoarthritis and other chronic inflammatory diseases. It can also serve as an indicator of how far the disease has progressed.

“Our results established a new, quantitative method for the assessment of a significant molecular biomarker that bridges a gap in the conventional technology,” said lead author Adam R. Hall, Ph.D., assistant professor of biomedical engineering at Wake Forest School of Medicine, part of Wake Forest Baptist.

“The sensitivity, speed and small sample requirements of this approach make it attractive as the basis for a powerful analytic tool with distinct advantages over current assessment technologies.”

The most widely used method is gel electrophoresis, which is slow, messy, semi-quantitative, and requires a lot of starting material, Hall said. Other technologies include mass spectrometry and size-exclusion chromatography, which are expensive and limited in range, and multi-angle light scattering, which is non-quantitative and has limited precision.

The study, which is published in the current issue of Nature Communications, was led by Hall and Elaheh Rahbar, Ph.D., of Wake Forest Baptist, and conducted in collaboration with scientists at Cornell University and the University of Oklahoma.

In the study, Hall, Rahbar and their team first employed synthetic HA polymers to validate the measurement approach. They then used the platform to determine the size distribution of as little as 10 nanograms (one-billionth of a gram) of HA extracted from the synovial fluid of a horse model of osteoarthritis.

The measurement approach consists of a microchip with a single hole or pore in it that is a few nanometers wide – about 5,000 times smaller than a human hair. This is small enough that only individual molecules can pass through the opening, and as they do, each can be detected and analyzed. By applying the approach to HA molecules, the researchers were able to determine their size one-by-one. HA size distribution changes over time in osteoarthritis, so this technology could help better assess disease progression, Hall said.

“By using a minimally invasive procedure to extract a tiny amount of fluid – in this case synovial fluid from the knee – we may be able to identify the disease or determine how far it has progressed, which is valuable information for doctors in determining appropriate treatments,” he said.

Hall, Rahbar and their team hope to conduct their next study in humans, and then extend the technology with other diseases where HA and similar molecules play a role, including traumatic injuries and cancer.

Here’s a link to and a citation for the paper,

Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor by Felipe Rivas, Osama K. Zahid, Heidi L. Reesink, Bridgette T. Peal, Alan J. Nixon, Paul L. DeAngelis, Aleksander Skardal, Elaheh Rahbar, & Adam R. Hall. Nature Communications volume 9, Article number: 1037 (2018) doi:10.1038/s41467-018-03439-x
Published online: 12 March 2018

This paper is open access.

Nanotechnology delivery system for skin disease therapies

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A Feb. 29, 2016 news item on ScienceDaily announces a new development concerning free radicals that may be helpful with skin diseases and pathologies,

Researchers at The Hebrew University of Jerusalem have developed a nanotechnology-based delivery system containing a protective cellular pathway inducer that activates the body’s natural defense against free radicals efficiently, a development that could control a variety of skin pathologies and disorders.

A Feb. 29, 2016 Hebrew University of Jerusalem press release on EurekAlert, which originated the news item, expands on the theme,

The human skin is constantly exposed to various pollutants, UV rays, radiation and other stressors that exist in our day-to-day environment. When they filter into the body they can create Reactive Oxygen Species (ROS) – oxygen molecules known as Free Radicals, which are able to damage and destroy cells, including lipids, proteins and DNA.

In the skin – the largest organ of the body – an excess of ROS can lead to various skin conditions, including inflammatory diseases, pigmenting disorders, wrinkles and some types of skin cancer, and can also affect internal organs. This damage is known as Oxidative Stress.

The body is naturally equipped with defense mechanisms to counter oxidative stress. It has anti-oxidants and, more importantly, anti-oxidant enzymes that attack the ROS before they cause damage.

In a review article published in the journal Cosmetics, a PhD student from The Hebrew University of Jerusalem, working in collaboration with researchers at the Technion – Israel Institute of Technology, suggested an innovative way to invigorate the body to produce antioxidant enzymes, while maintaining skin cell redox balance – a gentle equilibrium between Reactive Oxygen Species and their detoxification.

“The approach of using the body’s own defense system is very effective. We showed that activation of the body’s defense system with the aid of a unique delivery system is feasible, and may leverage dermal cure,” said Hebrew University researcher Maya Ben-Yehuda Greenwald.

Ben-Yehuda Greenwald showed that applying nano-size droplets of microemulsion liquids containing a cellular protective pathway inducer into the skin activates the natural skin defense systems.

“Currently, there are many scientific studies supporting the activation of the body’s defense mechanisms. However, none of these studies has demonstrated the use of a nanotechnology-based delivery system to do so,” Ben-Yehuda Greenwald said.

Production of antioxidant enzymes in the body is signaled in the DNA by activation of Nrf2 – a powerful protein that exists in every cell in our body. This Nrf2 cellular-protective signaling pathway is a major intersection of many other signaling pathways affecting each other and determining cell functionality and fate. Nrf2 is capable of coordinating the cellular response to internal as well as external stressors by tight regulation of phase-II protective enzymes, such as the antioxidant enzymes.

Ben-Yehuda Greenwald has also discovered a new family of compounds capable of activating the Nrf2 pathway. Moreover, by incorporating them into the unique delivery system she has developed, she managed to efficiently stimulate the activation of the Nrf2 pathway and mimic the activity of the body’s’ natural way of coping with a variety of stress conditions.

“The formula we have created could be used in topical medication for treating skin conditions. Our formula could be used both as preventive means and for treatment of various skin conditions, such as infections, over-exposure to UV irradiation, inflammatory conditions, and also internal disease,” she said.

While the researchers focused on the skin, the formulation could prove to be effective in enhancing the body’s natural protection against the damaging effects of ROS in other parts of the body, such as inflammation in cardiovascular diseases, heart attack, cancer, multiple sclerosis and Alzheimer’s.

Here’s an image provided by Ben-Yehuda Greenwald illustrating the team’s work,

Caption: These are the consequences of skin exposure to stressors. Credit: Maya Ben-Yehuda Greenwald

Caption: These are the consequences of skin exposure to stressors. Credit: Maya Ben-Yehuda Greenwald

Here’s a link to and a citation for the paper,

Skin Redox Balance Maintenance: The Need for an Nrf2-Activator Delivery System by Maya Ben-Yehuda Greenwald, Shmuel Ben-Sasson, Havazelet Bianco-Peled, and Ron Kohen. Cosmetics 2016, 3(1), 1; doi:10.3390/cosmetics3010001 Published: 15 January 2016

This paper appears to be open access.