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Scientists Discover Protein Partners that Could Heal Heart Muscle

A protein that helps make neurons also works to reprogram scar tissue cells into heart muscle cells, especially in partnership with a second protein, according to a study led by Li Qian, PhD, at the UNC School of Medicine.

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A protein that helps make neurons also works to reprogram scar tissue cells into heart muscle cells, especially in partnership with a second protein, according to a study led by Li Qian, PhD, at the UNC School of Medicine.
Credit: Qian Lab, UNC School of Medicine
Human fibroblasts reprogrammed into cardiomyocyte-like cells. Immunofluorescence shows different molecules: DNA (blue), cardiac Troponin T (orange) and αActinin (green).
« Scientists Discover Protein Partners that Could Heal Heart Muscle

Newswise — CHAPEL HILL, N.C. – Scientists at the UNC School of Medicine have made a significant advance in the promising field of cellular reprogramming and organ regeneration, and the discovery could play a major role in future medicines to heal damaged hearts.

In a study published in the journal Cell Stem Cell, scientists at the University of North Carolina at Chapel Hill discovered a more streamlined and efficient method for reprogramming scar tissue cells (fibroblasts) to become healthy heart muscle cells (cardiomyocytes). Fibroblasts produce the fibrous, stiff tissue that contributes to heart failure after a heart attack or because of heart disease. Turning fibroblasts into cardiomyocytes is being investigated as a potential future strategy for treating or even someday curing this common and deadly condition.

Surprisingly, the key to the new cardiomyocyte-making technique turned out to be a gene activity-controlling protein called Ascl1, which is known to be a crucial protein involved in turning fibroblasts into neurons. Researchers had thought Ascl1 was neuron-specific.

“It’s an outside-the-box finding, and we expect it to be useful in developing future cardiac therapies and potentially other kinds of therapeutic cellular reprogramming,” said study senior author Li Qian, PhD, associate professor in the UNC Department of Pathology and Lab Medicine and associate director of the McAllister Heart Institute at UNC School of Medicine.

Scientists over the last 15 years have developed various techniques to reprogram adult cells to become stem cells, then to induce those stem cells to become adult cells of some other type. More recently, scientists have been finding ways to do this reprogramming more directly – straight from one mature cell type to another. The hope has been that when these methods are made maximally safe, effective, and efficient, doctors will be able to use a simple injection into patients to reprogram harm-causing cells into beneficial ones.

“Reprogramming fibroblasts has long been one of the important goals in the field,” Qian said. “Fibroblast over-activity underlies many major diseases and conditions including heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, and the scar-like brain damage that occurs after strokes.”

In the new study, Qian’s team, including co-first-authors Haofei Wang, PhD, a postdoctoral researcher, and MD/PhD student Benjamin Keepers, used three existing techniques to reprogram mouse fibroblasts into cardiomyocytes, liver cells, and neurons. Their aim was to catalogue and compare the changes in cells’ gene activity patterns and gene-activity regulation factors during these three distinct reprogrammings.

Unexpectedly, the researchers found that the reprogramming of fibroblasts into neurons activated a set of cardiomyocyte genes. Soon they determined that this activation was due to Ascl1, one of the master-programmer “transcription factor” proteins that had been used to make the neurons.

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Since Ascl1 activated cardiomyocyte genes, the researchers added it to the three-transcription-factor cocktail they had been using for making cardiomyocytes, to see what would happen. They were astonished to find that it dramatically increased the efficiency of reprogramming – the proportion of successfully reprogrammed cells – by more than ten times. In fact, they found that they could now dispense with two of the three factors from their original cocktail, retaining only Ascl1 and another transcription factor called Mef2c.

In further experiments they found evidence that Ascl1 on its own activates both neuron and cardiomyocyte genes, but it shifts away from the pro-neuron role when accompanied by Mef2c. In synergy with Mef2c, Ascl1 switches on a broad set of cardiomyocyte genes.

“Ascl1 and Mef2c work together to exert pro-cardiomyocyte effects that neither factor alone exerts, making for a potent reprogramming cocktail,” Qian said.

The results show that the major transcription factors used in direct cellular reprogramming aren’t necessarily exclusive to one targeted cell type.

Perhaps more importantly, they represent another step on the path towards future cell-reprogramming therapies for major disorders. Qian says that she and her team hope to make a two-in-one synthetic protein that contains the effective bits of both Ascl1 and Mef2c, and could be injected into failing hearts to mend them.

“Cross-lineage Potential of Ascl1 Uncovered by Comparing Diverse Reprogramming Regulatomes” was co-authored by Haofei Wang, Benjamin Keepers, Yunzhe Qian, Yifang Xie, Marazzano Colon, Jiandong Liu, and Li Qian.

Funding was provided by the American Heart Association and the National Institutes of Health (T32HL069768, F30HL154659, R35HL155656, R01HL139976, R01HL139880).

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Source:  University of North Carolina School of Medicine

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Lifestyle

Keep Cold and Flu Season at Bay

During cold and flu season, preparation and proper treatment are crucial for recovery, minimizing illness spread, and maintaining overall health.

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Cold and Flu

(Family Features) It doesn’t take much for cold and flu symptoms to take over. Even a mild case of the sniffles can make it difficult to navigate the demands of everyday life. It’s virtually impossible to avoid germs altogether, but you can make sure you’re ready to fight off an infection, whether it’s a minor cold or a full-blown case of the flu.

Cold and Flu Tips

“I always share a few easy and simple methods with my patients when cold and flu season comes back around to keep them in the best shape,” said Dr. Tim Tiutan, board-certified internal medicine physician. “Not only does getting ahead offer protection, but knowing what to do when symptoms start to come on, and what to have in your medicine cabinet, can help ease the burden of an oncoming illness.”

Preparation and prevention play important roles before a bug hits, but it’s also valuable to know how to effectively treat an illness and keep your loved ones from getting sick.

Prevent
Short of stashing yourself away in a bubble, there aren’t many failsafe ways to fully avoid germs. However, some basic hygiene and preventive care can go a long way toward minimizing your risk. Regularly washing your hands can help get rid of germs before you accidentally introduce them to your eyes, mouth or nose. Be especially diligent after spending time in crowded places.

Maintaining an overall healthy lifestyle also helps ensure you’re in optimal condition if you do get sick. That means eating a nutritious, well-rounded diet and keeping up with your exercise routine. Also be sure to talk to your doctor or pharmacist about getting a flu shot; while it may not fully prevent you from getting sick, in most cases it helps your body fight back and keeps your symptoms manageable.

Prepare
Knowing you can’t completely eliminate your exposure to germs, it’s a good idea to ensure you have everything you need to fight a cold or flu on hand. At least once a year, give your medicine cabinet a thorough cleaning. Discard any expired medications and replace products that have run low, especially those designed to help fight symptoms like pain relievers, fever reducers, decongestants, antihistamines and cough syrups.

It’s also a good time to restock items like tissues, cough drops, hand sanitizer and antibacterial soap. Medical supplies like thermometers and humidifiers also come in handy when you’re under the weather; check to be sure yours are in good working order and consider adding any supplies you don’t already have, such as a blood pressure cuff or home oximeter.

Treat
Once you’re sick, sleep is one of the best remedies. Your body can redirect energy toward healing when you’re sleeping, which helps boost your immune system, so give yourself permission to rest when you’re feeling down.

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In addition to getting enough rest, it’s important to treat your symptoms, not just mask them. Because symptoms like fever, runny nose, chest congestion, cough and more can indicate a more serious problem, finding the root cause of the symptoms can be a more effective treatment strategy.

For example, some common remedies for chest congestion only mask the symptoms. Many doctors recommend an option like Mucinex 12-Hour because it treats the cause of chest congestion by thinning and loosening excess mucus. One dose lasts up to 12 hours, helping you clear mucus and relieve chest congestion.

Contain
Getting rest and managing your symptoms are easier when you stay at home, but it’s also the best way to prevent spreading germs to others. It’s not always practical, but if you can, limit yourself to one area of the house, away from family members. Cough into your elbow or a tissue, never your hands. Use antibacterial hand sanitizer and wipe down surfaces to minimize others’ contact with your germs.

Be especially wary of spending time with anyone who has a compromised immune system while you’re contagious, including those with pre-existing conditions, older adults and pregnant women. Take advantage of delivery or curbside services for essentials like groceries and talk with your employer about working remotely or using sick time until you’re feeling better.

Find more advice to help fight this cold and flu season at Mucinex.com. https://www.youtube.com/embed/zUpFn6VhRTM?feature=share/?utm_source=familyfeatures&utm_medium=referral&utm_campaign=#17187-Mucinex

When to Call for Help if You’re Feeling Lousy

If you’re experiencing cold symptoms, you might wonder when it’s appropriate to see a doctor for further evaluation. While most colds resolve on their own within a week or two, there are certain instances when seeking medical attention is advisable.

High Fever: If your fever persists for more than three days or reaches 102 F or higher, consult a health care provider.

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Persistent or Severe Headaches: If you experience persistent or severe headaches that are not alleviated by over-the-counter medication, it’s advisable to consult a health care provider, as this could indicate a more serious underlying issue.

Persistent Symptoms: If your symptoms worsen or don’t improve after a week, seek medical advice.

Unusual Symptoms: If you experience uncommon or concerning symptoms during a cold, such as extreme fatigue, confusion, dehydration or a high fever that doesn’t respond to treatment, consult your doctor promptly for a proper diagnosis and treatment plan.

Trouble Breathing: Difficulty breathing, chest pain or wheezing can indicate a more severe respiratory condition and warrant medical attention.

High-Risk Individuals: For individuals at high risk of complications from colds, such as pregnant women, the elderly or individuals with conditions like diabetes or heart disease, it’s important to seek advice early to prevent any potential complications.

Remember, your health care provider can offer guidance tailored to your specific situation, helping you manage your cold effectively and ensure optimal recovery.

Photos courtesy of Shutterstock

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Visit our Food & Drink section to get the latest on Foodie News and recipes, offering a delightful blend of culinary inspiration and gastronomic trends to elevate your dining experience.

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Lifestyle

Self-forgiveness is more than self-comfort − a philosopher explains

Self-forgiveness requires confronting negative emotions, acknowledging wrongdoing, and is essential for moral growth and healthier relationships.

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forgiveness
Forgiving yourself can be a sign of moral growth − but only if you put in the work. Stephanie Verhart/E+ via Getty Images

Mordechai Gordon, Quinnipiac University

As the Jewish High Holidays approach, which begin with Rosh Hashanah and continue with Yom Kippur, the theme of forgiveness keeps coming to my mind.

The 10 days from Rosh Hashanah to Yom Kippur are referred to in the Jewish tradition as the days of repentance, or the days of awe. During this period, Jews who observe the holidays implore God to respond to their sins with mercy, while also requesting forgiveness from anyone those individuals may have wronged in the past year.

Most conversations about forgiveness focus on the meaning and value of forgiving others. Douglas Stewart, a philosopher of education who has researched forgiveness extensively, writes that to forgive implies a willingness to let go of our negative emotions or hard feelings and to adopt in their place a more generous and compassionate attitude toward our wrongdoers.

Other philosophers have pointed out that the benefits of forgiveness include overcoming resentment, restoring relationships and setting a wrong to rest in the past – without vengeance. As such, to forgive should be considered morally valuable and admirable.

But what about self-forgiveness? Is it morally valuable, or just something we do to make ourselves feel better? And what is self-forgiveness, anyway?

As a philosopher of education, some of my own research has wrestled with these questions.

A man with white hair and a red polo shirt throws small white pieces of bread over a wooden bridge into a stream below.
During Tashlich, a ceremony on Rosh Hashanah, people symbolically cast away their sins by throwing bits of bread into flowing water. Bill Greene/The Boston Globe via Getty Images

Defining self-forgiveness

Self-forgiveness means managing to work through painful feelings such as guilt, shame and deep disappointment with ourselves. It entails transforming negative attitudes, such as contempt, anger and shame, into more positive emotions such as respect and humility.

It is important to recognize, however, that a wrongdoer cannot simply reject shame: They must confront it. Moral philosophers such as Byron Williston assert that people who have deeply wronged others, such as betraying a loved one, need to experience shame and take responsibility for their actions – such as asking for forgiveness. Otherwise, an attempt at self-forgiveness is not likely to be meaningful.

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Finally, we need to keep in mind that self-forgiveness does not imply someone has extinguished all the negative feelings directed at themselves or is done with self-reproach. This would amount to an impossible goal.

Rather, as philosopher Robin Dillon pointed out, self-forgiveness suggests that someone is no longer being consumed or overwhelmed by those negative feelings. In short, it is possible to forgive ourselves and still view ourselves with a demanding and critical eye.

Moral development

Getting there, though, is not easy. Self-forgiveness entails working through a rigorous process of coming to terms with wrongdoing.

According to ethicist Margaret Holmgren, that process includes at least four steps: acknowledging that what we did was wrong; coming to terms with why it was wrong; allowing ourselves to experience grief and self-resentment at having injured another person; and, finally, making a genuine effort to correct the attitudes that led to the harmful act and making amends to the victim.

In other words, confronting negative emotions, attitudes and patterns is essential prior to attempting to restore relationships with others. Only once we are able to relax the preoccupation with guilt and shame, and to genuinely forgive ourselves, can we meaningfully contribute to relationships as liberated and equal partners – especially in ongoing ones, such as with family and friends.

A close-up photo of two people clutching both of each other's hands.
Self-forgiveness isn’t just self-serving. Jasmin Merdan/Moment via Getty Images

Of course, there are cases in which the offense is so vast, such as genocide, that no individual can make full restitution or provide an adequate apology for the wrong.

There are other times when an apology is impossible. Perhaps victims are dead; perhaps a direct apology would retraumatize them or do more harm than good.

In those cases, I would argue, an offender can still attempt to work toward self-forgiveness – acknowledging not only the victim’s intrinsic worth but their own, regardless of their ability to make amends. This in itself is moral growth: appreciating that neither is a mere object that can be manipulated or abused.

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The take-home point, I would argue, is that going through the process of self-forgiveness is morally beneficial. It can not only liberate people who tend to reproach themselves incessantly, but it can enhance their ability to relate ethically toward others – to acknowledge wrongdoing, while simultaneously affirming their own value.

Most people have experienced at least one situation in which they inflicted pain on someone else and recognized that their words or actions caused harm. In such situations, we also often feel ashamed of ourselves and attempt to apologize or make amends.

Yet I hope that during this High Holiday season we keep in mind that self-forgiveness should also be considered essential. If moral development means a process in which our self-awareness and character mature, then acknowledging wrongdoing and experiencing shame, followed by self-forgiveness, are indispensable for that process.

Mordechai Gordon, Professor of Education, Quinnipiac University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.

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health and wellness

Protecting Your Lung Health at Any Age

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Lung Health

(Family Features) Chronic obstructive pulmonary disease, or COPD, is a serious lung condition that makes breathing difficult. Whether you’re a younger adult, middle-aged or over 60, you can take steps to protect your lungs or manage your COPD to feel better, be more active and breathe easier. Follow these tips from the National Heart, Lung, and Blood Institute to bring your lung health into focus – at any age. Learn more at nhlbi.nih.gov/BreatheBetter.


SOURCE:
National Heart, Lung, and Blood Institute

Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.


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