Image Credit: National Human Genome (Flickr)

Cells Become Zombies When the Ends of their Chromosomes are Damaged – a Tactic Both Helpful and Harmful for Health

Damage to the ends of your chromosomes can create “zombie cells” that are still alive but can’t function, according to our recently published study in Nature Structural and Molecular Biology.

When cells prepare to divide, their DNA is tightly wound around proteins to form chromosomes that provide structure and support for genetic material. At the ends of these chromosomes are repetitive stretches of DNA called telomeres that form a protective cap to prevent damage to the genetic material. However, telomeres shorten each time a cell divides. This means that as cells divide more and more as you age, your telomeres become increasingly shorter and more likely to lose their ability to protect your DNA.

Telomeres serve as protective caps at the ends of each chromosome.

Damage to genetic material can lead to mutations that cause cells to divide uncontrollably, resulting in cancer. Cells avoid becoming cancerous when their telomeres become too short after dividing too many times and potentially accruing damage along the way, however, they do this by entering a zombielike state that stops cells from dividing through a process called cellular senescence.

Because they are resistant to death, senescent – or “zombie” – cells accumulate with age. They can be beneficial to health by promoting senescence in nearby cells at risk of becoming cancerous and attracting immune cells to clear out cancer cells. But they can also contribute to disease by impairing tissue healing and immune function, and by secreting chemicals that promote inflammation and tumor growth.

We wanted to know if direct damage to telomeres can be sufficient to trigger senescence and make zombie cells. In order to figure this out, we needed to confine damage just to the telomeres. So we attached a protein to the telomeres of human cells grown in the lab. Then we added a dye to the protein that makes it sensitive to light. Shining a far-red light (or light with a wavelength slightly shorter than infrared light) on the cells induces the protein to produce oxygen free radicals – highly reactive molecules that can damage DNA – right at the telomeres, sparing the rest of the chromosome and the cell.

We found that direct damage to the telomeres was sufficient to turn cells into zombies, even when these protective caps weren’t shortened. The reason for this, we discovered, was likely a result of disrupted DNA replication at the telomeres that leaves chromosomes even more susceptible to damage or mutations.

The telomeres (green) at the tips of chromosomes (blue) damaged by free radicals become fragile (green arrows) and trigger senescence. Ryan Barnes/Opresko Lab

Why it Matters

Telomeres naturally shorten with age. They limit how many times a cell can divide by signaling cells to become zombies when they reach a certain length. But an excess of free radicals produced from both normal bodily processes as well as exposure to harmful chemicals like air pollution and tobacco smoke can lead to a condition called oxidative stress that can accelerate telomere shortening. This can prematurely trigger senescence and contribute to age-related diseases, including immunodeficiency, cardiovascular disease, metabolic disease and cancer.

Our study reveals that telomeres not only serve as alarm clocks that indicate a cell divided too many times, but also as warning bells for harmful levels of oxidative stress. Age-related shortening of telomeres isn’t the only thing that triggers senescence; telomere damage is also sufficient to turn a cell into a zombie.

What Other Research is Being Done

Researchers are studying treatments and interventions that can protect telomeres from damage and prevent zombie cell accumulation. A number of studies in mice have found that removing zombie cells can promote healthy aging by improving cognitive function, muscle mass and function and recovery from viral infections.

Researchers are also developing drugs called senolytics that can either kill zombie cells or prevent them from developing in the first place.

What’s Next

This study focuses on the consequences of telomere damage in actively dividing cells, like kidney and skin cells. We’re now looking at how this damage will play out in cells that don’t divide, like neurons or heart muscle cells. While researchers have shown that the telomeres of nondividing cells and tissues become more dysfunctional with age, it’s unclear why this happens when these telomeres should not be shortening in the first place.

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Image Credit: Diverse Stock Photos (Flickr)

Why are Drug Names So Long and Complicated? A Pharmacist Explains the Logic Behind the Nomenclature

At some point in your life, you’ll likely find yourself with a prescription from your doctor to fill. While it’s important to keep track of all the medications you’re taking, that can be hard to do when the names of so many of these drugs are difficult to pronounce and even harder to remember.

In my role as a pharmacist, I’ve helped countless patients figure out exactly which medication they were taking for what ailment. Some wonder why they were prescribed the medication in the first place, or need help differentiating between drugs with names that seem like complete gibberish.

But there is a rhyme and a reason to drug names. All prescribed medications follow a standard nomenclature that describes what the drug is made of and how it functions.

Who Names Drugs?

Drugs get both a brand, or proprietary, name and a generic name that is nonproprietary. Each is assigned in a slightly different process.

As long as a drug compound isn’t trademarked, drug companies decide on a proprietary brand name for the medications they sell. Usually the brand name relates to the conditions the drug is intended to treat and is easy for both providers and patients to remember but doesn’t follow a standardized naming guideline. For example, the drug Lopressor helps lower blood pressure.

On the other hand, generic drug names all follow a standard nomenclature that helps medical providers and researchers more easily recognize and classify the drug. Lopressor, for example, has a generic name of metoprolol tartrate. The U.S. Adopted Names Council, composed of representatives from the Food and Drug Administration, American Medical Association, U.S. Pharmacopeia and American Pharmacists Association, works with the World Health Organization to assign international nonproprietary names, or INNs, to drug compounds. Similar organizations exist internationally.

A globally recognized naming process makes an otherwise confusing name game more manageable. It helps the medical community easily learn and categorize newly approved medications and reduce prescribing errors by providing a unique, standard name that reflects each active ingredient in the drug.

For example, several Type 2 diabetes medications fall under one class called glucagon-like peptide-1 (GLP-1) receptor agonists. Although all medications in this class have different brand names, each of the generic versions ends in the suffix “-tide.” This helps health providers identify all the drugs that belong to this medication class. A few examples include Byetta (exenatide), Trulicity (dulaglutide) and Victoza (liraglutide).

How are Generic Drug Names Assigned?

The naming process starts when a drug company submits an application to the U.S. Adopted Names Council with a proposed generic name. USAN considers a number of factors when evaluating a name, such as whether it relates to how the drug works, how translatable it is to other languages and whether it is easy to say. In general, the name should be simple – fewer than four syllables long – and should not be easily confused with other existing generic drugs.

Once a name is agreed upon by USAN and the drug company, it is then proposed to the INN Expert Group. Sponsored by the World Health Organization, the INN Expert Group is composed of global specialists who represent the pharmaceutical, chemical, pharmacological and biochemical sciences. They may either accept the proposed name or suggest an alternative. Once the drug company, USAN and the INN Expert Group come to an agreement about a name, it is placed in the WHO Drug Information journal for four months for public comments or objections before final adoption.

What’s in a Generic Drug Name?

Generic names follow a prefix-infix-stem system. The prefix helps distinguish a drug from other drugs in the same class. The infix, used more occasionally, further subclassifies the drug. The stem at the very end of the name indicates the drug’s function and marks its place within the name game.

Stems are composed of one or two syllables that describe a drug’s biological effects as well as its physical and chemical qualities and structure. Drugs with the same stem share features like the conditions they treat and how they work in the body. The WHO publishes a regularly updated stem book to keep everything in line.

For example, the stem “-prazole” indicates that the drug is chemically related to a class of compounds called benzimidazoles that have similar functions. As a result, drugs such as lansoprazole (Prevacid), esomeprazole (Nexium) and omeprazole (Prilosec) all treat acid reflux, ulcers and heartburn. The “e” prefix of esomeprazole differentiates it from omeprazole, which has a slightly different chemical structure.

Another common example is drugs that use the stem “stat,” which means enzyme inhibitors. Atorvastatin (Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor) all belong to the same class of inhibitors that block a key enzyme in the body’s cholesterol production process. As a result, these cholesterol-reducing “statins” are used to prevent cardiovascular conditions like heart attack and stroke.

Are There Exceptions to the Name Game?

Although generic names stay consistent, there have been multiple changes to brand names over the past couple of decades after increases in prescribing and dispensing errors. Some examples include the acid reflux and stomach ulcer drug omeprazole, which was rebranded from Losec to Prilosec because it was frequently confused with the diuretic Lasix. Another example is when the antidepressant Brintellix was changed to Trintellix because it was commonly confused with the blood thinner Brilinta.

Some generic medications may work at multiple targets in the body and be used for multiple conditions. For example, drugs with the stem “-afil,” such as tadalafil (Cialis), sidenafil (Viagra) and vardenafil (Levitra), belong to a class of drugs that relax smooth muscle and widen the blood vessels. Although commonly prescribed for erectile dysfunction, they can also be used to treat pulmonary arterial hypertension, a specific type of elevated blood pressure that affects the arteries in the heart and lungs.

In addition, nomenclature guidelines
aren’t set in stone, and the U.S. Adopted Names Council anticipates that they
will continue to change as newer, more complex substances are discovered, developed
and marketed.

For example, a rise in the number of drugs developed with different salts and esters has led to the use of a modified naming process to incorporate the inactive parts of the compound.

As you can guess, it takes health care providers countless months and years to learn and understand this naming process. We are taught the science behind each chemical structure and how it works, which makes it easier to know the rules of the name game. But for those without a background in chemistry and biology, it can be like reading a foreign language.

There are several resources that can help you navigate the drug name game, however. Ask your health care provider or pharmacist if you have questions about how your medication works or what it is used for. They are generally a phone call or visit away.

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NexusBioAg and MustGrow Biologics Announce Exclusive Marketing and Distribution Agreement in Canada

Research, News, and Market Data on MustGrow Biologics

Collaboration expands
innovative, sustainable and regenerative farming solutions for Canadian growers

Downers Grove, ILL. & SASKATOON, SASK. — July 20, 2022 — Univar Solutions Inc. (NYSE: UNVR) (“Univar
Solutions“),  a leading global solutions provider to users of specialty ingredients and chemicals, announced today that NexusBioAg, a division of Univar Solutions, and MustGrow Biologics Corp. (CSE: MGRO) (OTC: MGROF) (FRA: 0C0) (“MustGrow“), an agricultural biotechnology company focused on providing science-based biological solutions for high-value crops, have reached an exclusive marketing and distribution agreement in the Canadian canola and pulse market for TerraMG™, a mustard-derived soil biopesticide technology. The addition of this plant-based technology further diversifies and expands NexusBioAg’s extensive portfolio of inoculants, micronutrients, nitrogen stabilizers and foliars for the Canadian agricultural market.

In 2021, NexusBioAg and MustGrow initiated a field research program to develop MustGrow’s sustainable farming technology in Canadian canola and pulse crops. This technology has the potential to address the agronomic challenges of ClubRoot and Aphanomyces diseases which impact these crops. Building on the past data, the companies now are moving forward to the next stage of the development process. Through this exclusive marketing and distribution agreement, NexusBioAg customers have access to the latest in agronomic innovation, which is yet to be registered with Canada’s Pest Management Regulatory Agency.

“TerraMG complements the NexusBioAg portfolio and we are excited to add this technology to our growing product offering. As the sole distributor of TerraMG in Canada for use in canola and pulse crops, this agreement further reinforces NexusBioAg’s commitment to collaborating with leading manufacturers to launch innovative, sustainable and cutting-edge solutions that provide value to the Canadian agricultural industry and benefit its growers,” said Matthew Ottaway, senior vice president, global consumer solutions for Univar Solutions.

NexusBioAg is committed to launching innovative, cutting-edge products, with a focus on sustainability and regenerative agriculture, which benefit the Canadian agricultural industry and growers. MustGrow specializes in the research and development of organic biopesticides, harnessing the mustard seed’s natural defense mechanism with a technology that has the potential to control diseases, pests and weeds. Combining the proficiencies of both companies in the agriculture market will help Canadian growers benefit from innovative and sustainable farming solutions.

“We are very pleased to partner with an organization like NexusBioAg. Their team’s technical and commercial expertise is unparalleled and will be advantageous in accelerating the development and growth of TerraMG for use in Canadian canola and pulse crops. The NexusBioAg team has tremendous knowledge of the Canadian agriculture market as well as sustainable farming solutions. We look forward to commercializing this biopesticide technology in the Canadian market together,” remarked MustGrow COO Colin Bletsky.

For more information about NexusBioAg’s crop nutrition solutions, please visit nexusbioag.com. To learn more about TerraMG™, visit mustgrow.ca.

About Univar Solutions
Univar Solutions (NYSE: UNVR) is a leading global chemical and ingredient distributor representing a premier portfolio from the world’s leading producers. With the industry’s largest private transportation fleet and technical sales force, unparalleled logistics know-how, deep market and regulatory knowledge, formulation and recipe development, and leading digital tools, Univar Solutions is well-positioned to offer tailored solutions and value-added services to a wide range of markets, industries, and applications. While fulfilling its purpose to help keep communities healthy, fed, clean and safe, Univar Solutions is committed to helping customers and suppliers innovate and focus on Growing Together. Learn more at univarsolutions.com.

About NexusBioAg
Univar Solutions’ NexusBioAg provides an expanded portfolio of crop nutrition solutions, including industry-leading inoculants, micronutrients, nitrogen stabilizers, and foliar products. With a diverse collection of inventory and logistics experts, procurement, customer service, agronomists, and sales and marketing experts, NexusBioAg strives to help meet increasingly unique agricultural businesses’ needs. Through these best-in-class capabilities, a collaborative team-oriented approach, and a commitment to agricultural integrity, NexusBioAg is helping customers innovate and grow. Learn more at NexusBioAg.com.

About MustGrow
MustGrow is an agriculture biotech company developing organic biopesticides and bioherbicides by harnessing the natural defense mechanism of the mustard plant to protect the global food supply from diseases, insect pests, and weeds. MustGrow and its leading global partners — Janssen (pharmaceutical division of Johnson & Johnson), Bayer, Sumitomo Corporation, and Univar Solutions’ NexusBioAg — are developing mustard-based organic solutions to potentially replace harmful synthetic chemicals. Over 100 independent tests have been completed, validating MustGrow’s safe and effective approach to crop and food protection. Pending regulatory approval, MustGrow’s patented liquid products could be applied through injection, standard drip or spray equipment, improving functionality and performance features. Now a platform technology, MustGrow and its global partners are pursuing applications in several different industries from preplant soil treatment and weed control, to postharvest disease control and food preservation. MustGrow has approximately 49.2 million basic common shares issued and outstanding and 55.1 million shares fully diluted. For further details please visit mustgrow.ca.  

Univar Forward-Looking Statements
This press release includes certain statements relating to future events and Univar Solutions’ intentions, beliefs, expectations, and predictions for the future, which are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are subject to known and unknown risks and uncertainties, many of which may be beyond Univar Solutions’ control. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from the expectations and assumptions. A detailed discussion of these factors and uncertainties is contained in Univar Solutions’ filings with the Securities and Exchange Commission. Potential factors that could affect such forward-looking statements include, among others: the ultimate geographic spread of the COVID-19 pandemic; the duration and severity of the COVID-19 pandemic; actions that may be taken by governmental authorities to address or otherwise mitigate the impact of the COVID-19 pandemic; the potential negative impacts of COVID-19 on the global economy and Univar Solutions’ customers and suppliers; the overall impact of the COVID-19 pandemic on Univar Solutions’ business, results of operations and financial condition; other fluctuations in general economic conditions, particularly in industrial production and the demands of Univar Solutions’ customers; significant changes in the business strategies of producers or in the operations of Univar Solutions’ customers; increased competitive pressures, including as a result of competitor consolidation; significant changes in the pricing, demand and availability of chemicals; Univar Solutions’ levels of indebtedness, the restrictions imposed by Univar Solutions’ debt instruments, and Univar Solutions’ ability to obtain additional financing when needed; the broad spectrum of laws and regulations that we are subject to, including extensive environmental, health and safety laws and regulations; an inability to integrate the business and systems of companies we acquire, including of Nexeo Solutions, Inc., or to realize the anticipated benefits of such acquisitions; potential business disruptions and security breaches, including cybersecurity incidents; an inability to generate sufficient working capital; increases in transportation and fuel costs and changes in Univar Solutions’ relationship with third party providers; accidents, safety failures, environmental damage, product quality and liability issues and recalls; major or systemic delivery failures involving Univar Solutions’ distribution network or the products we carry; operational risks for which we may not be adequately insured; ongoing litigation and other legal and regulatory risks; challenges associated with international operations; exposure to interest rate and currency fluctuations; potential impairment of goodwill; liabilities associated with acquisitions, ventures and strategic investments; negative developments affecting Univar Solutions’ pension plans and multi-employer pensions; labor disruptions associated with the unionized portion of Univar Solutions’ workforce; and the other factors described in Univar Solutions’ filings with the Securities and Exchange Commission. We caution you that the forward-looking information presented in this press release is not a guarantee of future events or results and that actual events or results may differ materially from those made in or suggested by the forward-looking information contained in this press release. In addition, forward-looking statements generally can be identified by the use of forward-looking terminology such as “may,” “plan,” “seek,” “will,” “expect,” “intend,” “estimate,” “anticipate,” “believe” or “continue” or the negative thereof or variations thereon or similar terminology. Any forward-looking information presented herein is made only as of the date of this press release, and Univar Solutions does not undertake any obligation to update or revise any forward-looking information to reflect changes in assumptions, the occurrence of unanticipated events, or otherwise, except as required by law.

MustGrow Forward-Looking Statements
Certain statements included in this news release constitute “forward-looking statements” which involve known and unknown risks, uncertainties and other factors that may affect the results, performance or achievements of MustGrow.

Generally, forward-looking information can be identified by the use of forward-looking terminology such as “plans”, “expects”, “is expected”, “budget”, “estimates”, “intends”, “anticipates” or “does not anticipate”, or “believes”, or variations of such words and phrases or statements that certain actions, events or results “may”, “could”, “would”, “might”, “occur” or “be achieved”. Examples of forward-looking statements in this news release include, among others, statements MustGrow makes regarding: (i) potential product approvals; (ii) anticipated actions by partners to drive field development work including dose rates, application frequency, application methods, and the regulatory work necessary for commercialization; (iii) expected product efficacy of MustGrow’s mustard-based technologies; and (iv) expected outcomes from collaborations with commercial partners.

Forward-looking statements are subject to a number of risks and uncertainties that may cause the actual results of MustGrow to differ materially from those discussed in such forward-looking statements, and even if such actual results are realized or substantially realized, there can be no assurance that they will have the expected consequences to, or effects on, MustGrow. Important factors that could cause MustGrow’s actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: (i) the preferences and choices of agricultural regulators with respect to product approval timelines; (ii) the ability of MustGrow’s partners to meet obligations under their respective agreements; and (iii) other risks described in more detail in MustGrow’s Annual Information Form for the year ended December 31, 2021 and other continuous disclosure documents filed by MustGrow with the applicable securities regulatory authorities which are available at www.sedar.com. Readers are referred to such documents for more detailed information about MustGrow, which is subject to the qualifications, assumptions and notes set forth therein.

This release does not constitute an offer for sale of, nor a solicitation for offers to buy, any securities in the United States.

Neither the CSE nor its Regulation Services Provider (as that term is defined in the policies of the CSE) accepts responsibility for the adequacy or accuracy of this release.

© 2022 MustGrow Biologics Corp. All rights reserved.